John Dorian, "J.D." to friends, is a boyishly handsome, self-deprecatingly funny, likeable guy who would be confident if he only realized his assets. Four years of medical school have prepared J.D. for his first day as an intern at Sacred Heart Hospital - but he has his doubts.
J.D. tries to persuade a smoker patient to quit smoking in order to impress Dr. Cox, who is just feeling lonely in his opinion. Elliot's attitude towards Carla annoys her, thus Turk is able to go on a date with Carla, when he convinces her to forgive Elliot.
J.D. begins to feel distant from Turk, when he leaves him abandoned every time that he tries to talk to him. Elliot fights with Kelso for calling her "sweetheart," and she seeks Dr. Cox's advice. J.D.'s relationship with Elliot goes in a time race, when he has 48 hours to kiss her before he is put into her "Friend Zone."
The three interns are each assigned patients with various illnesses. Statistically speaking, one of the three is going to die. J.D.'s patient is 86 year old Mrs. Tanner, who is in renal failure. 20 year old David Morrison is Turk's hernia patient and Elliot's patient Mrs. Guerrero only speaks Spanish and might have lupus.
J.D. points out what seems to be a technical mistake to Dr. Kelso, but it was really an attempt of Dr. Cox to save a woman without insurance using a dead guy's insurance. Dr. Kelso and Dr. Cox show J.D. their different ways of looking at medicine. Meanwhile, the Janitor intimidates J.D., Elliot discovers the healing powers of her boobs and Turk gives Carla a pen he thought he took from the Lost and Found box.
Dr. Cox is still facing the threat of suspension, and coincidentally, J.D. is assigned to a special patient: Jordan Sullivan, an important board member. She is very demanding and J.D. ends up sleeping with her after he confronts her. Only he didn't know that she is Dr. Cox's ex-wife, and now the only one who can save J.D.'s mentor from being fired by the evil Dr. Kelso. Meanwhile, Elliot is assigned to take care of a shrink whose jaw has been wired shut, and for whom she ends up becoming a patient. Carla's mom makes a scandal after Turk spends the night at Carla's, and when she breaks her leg, Carla blames Turk for it.
J.D. has finally earned the spot as brightest student, but he's got competition: Nick Murdoch, who seems to be nicer, friendlier and has a better butt than him. But even J.D. can't hate the guy, for he is so nice. But he is surprised when he finds Nick sitting in a corner crying because he can't take the pressure of medical internship. Meanwhile, Turk is having problems at the operation table and doesn't tell Carla, who keeps bothering Dr. Cox about it. And Dr. Cox gives Turk a very unique suggestion on how to calm down before surgery.
J.D. and Turk become heroes after saving a cameraman's life on TV, while heading to a strip club. But Turk quickly becomes the target of a new publicity campaign led by Dr. Kelso, exploiting the hospital's diversity. Meanwhile, J.D. worries about his evaluation. Elliot is going out with Carla, but in the last minute she blows her off and later Elliot runs into her in a bar.
J.D. gets to see the hospital through the eyes of a patient when he's admitted for appendicitis. Elliot examines him and he tells everyone how cold and rough she is, which drives her crazy. J.D. doesn't want Turk to operate on him, which hurts Turk's feelings. Meanwhile, Dr. Cox is trying to show off to his mentor, Dr. Benson, the ex-chief of medicine, who is also a patient at the hospital. The only thing in his way is Dr. Kelso, who almost dismissed Dr. Benson prematurely.
J.D. begins a new relationship with Carla. J.D. gains a new nickname - "Scooter" - and his relationship with Nurse Carla evolves as he begins to out-distance her medical knowledge, while Turk trembles, when he learns that his secret lunch spot was claimed years ago by the territorial Dr. Kelso. Elsewhere, Dr. Cox gives Elliot the evil eye when she won't discharge a troublesome patient.
It's Christmas, and even though J.D. and the others don't really feel like celebrating, Turk makes a huge deal about it. But his faith and happiness are gone after a very busy night at the hospital.
Dr. Cox has J.D. videotape the birth of the child of one of his friends.
A woman slips and falls on the wet floor of the hospital. Afraid that she might sue the hospital, Dr. Kelso asks J.D. to stand by her and be friendly, so she won't sue them. But J.D. is very busy with Dr. Cox's 24-hour marathon to keep his ICU patients alive.
Elliot is desperate for some attention from Dr. Cox. Meanwhile, Turk snaps at Carla when she steals fries from his plate.
J.D. is frustrated when his budding romance with an ex-patient wilts as their dates are constantly interrupted by emergency calls, while the beastly Dr. Kelso becomes less fearsome to the wide-eyed interns, when Dr. Cox informs them how to avoid the blowhard's bite. In addition, a perplexed Carla and Turk deal with their first sexual intimacy complication.
Alex and Elliot argue over missing medication, and J.D. needs to choose sides.
Meanwhile, Dr. Kelso gives Carla a ride to work and she sees a totally different side of him. Turk develops a conflict with Dr. Cox after he finds out that Dr. Cox has secret feelings for Carla.
After going to bed and spending an entire day having sex, J.D. and Elliot go to work trying to hide their new secret romance, but everybody already knows it.
When a rampaging Dr. Cox suddenly shows up at his door in a strange funk, J.D. sees a possibility of a breakthrough in their relationship - until he learns that Cox loses control in almost an annual rite. Meanwhile, Turk elects to partner with Elliot on a research project so that he can maneuver her back with his buddy J.D., and Carla struggles to fulfill a comatose patient's final request - playing heavy metal music in his room.
J.D., Elliot and Turk are receiving their first medical students, and now they finally get a chance to see what it feels like to be on the other side. Turk's student is a very attractive young woman, to whom Dr. Cox is immediately attracted. But he doesn't know his way around women and needs Turk to give him a little help. J.D. doesn't know how to handle his student and Elliot's turns out to the be son of an important CEO.
J.D. has a patient who's rude to him and the nurses and eventually dies from cancer. J.D. feels awful for not giving him his full attention and worries maybe he could have saved the guy if he was nicer to him.
Meanwhile, Elliot is convinced that Dr. Kelso is the one singing a song called "Tuscaloosa Heart" on a tape given to her by a patient who claims he went to college with Bob. And Dr. Cox finds himself trapped in a love square: He's falling in love with Kristen Murphy, his intern, just as his ex-wife reappears demanding sex – and there's also his crush on Carla.
An assortment of moms and dads descend on their offspring at home and in the workplace. J.D.'s father is a gregarious yet lonely divorcee who's desperately trying to be just one of the guys. Elliot's folks, on the other hand, are a snooty couple whose pompous behavior dismays their daughter. Similarly rattled is Turk, unnerved by the bonding of his girlfriend, Carla, and his brassy mother. But the most vexatious parent by far is the janitor's dad.
Turk's competitiveness is starting to annoy J.D., especially when it crosses the line of personal jokes and comes to patient's matters.
Meanwhile, Dr. Cox finally has a taste of good coffee, but thanks to his feud with Dr. Kelso, the only nurse who was able to make it gets fired. Elliot meets a very attractive patient, whom she instantly identifies, but has a really hard time getting him to ask her out.
J.D. fears being contaminated with Hepatitis B, after a needle accidentally sticks his forearm.
Meanwhile, Elliot has a hard time combining her new relationship and keeping up with studies. Turk obsesses about getting in shape, after Carla makes a fat joke about him.
Jordan's brother Ben is admitted at Sacred Heart for having an accident with a nail gun. J.D. learns that Ben has leukemia, but won't believe it, since there have been many mixups in the hospital lately, so he goes on a search for the real test results.
Ben takes the news of his diagnosis pretty well - at least better than his sister Jordan and J.D. Remarkably, it is Dr. Cox who is the voice of reason and compassion, until his own fears get in the way.
Meanwhile, Turk and Elliot have their own issues to deal with. Turk is upset because he wasn't chosen to assist on a difficult surgery and Elliot is criticized during rounds by Dr. Kelso for the 100th time.
It's J.D.'s last day as an intern, and soon he will become a resident. Carla and Turk are arguing about dating other people. Elliot finally rebels against being everyone's doormat, and J.D. is just trying to stay out of people's way.
Jordan has returned to get a physical and a new patient, Mr. Bober, has been admitted, because he needs his gall bladder removed. He really needs the surgery, but doesn't have the insurance to pay for it. They enlist the help of Dr. Cox, Dr. Wen and Jordan.