The episode picks up straight where "One of Our Own" left off. Horatio and Delko have arrived in Rio de Janeiro to hunt down Antonio Riaz, who ordered the hit on Marisol. The problem is that Horatio can't stop thinking about his late wife, and Brazilian authorities aren't being very cooperative. While there, Horatio runs into Yelina and finds out that Raymond is missing again. Ray Jr., now fourteen, teams up with Brazilian authorities and will stop at nothing to bring his father home safe, until Horatio learns the terrible truth... Raymond is already dead. Now Horatio must stop his nephew from getting himself killed trying to chase a ghost.
Calleigh is run off of the road in to a canal and causes freshly collected evidence to be compromised. The team must work to find new evidence, as most of the water-damaged evidence is unusable.
The dead body of a celebrity is found at an A-list party. They soon discover that the murder is linked to a “death pool,” where gambling occurs on an offshore ship. A counterfeit ring is also discovered where 100-dollar bills are produced in this 100th episode of CSI: Miami.
The body of a local politician is found in an empty house. The entire neighborhood was upset that he was backing the use of eminent domain, allowing the government to force them out of their homes.
When strange accidents occur in the lab, the CSI team is spooked during a death investigation involving voodoo. As Halloween is near everyone starts to think that the lab is cursed.
After an accident where the driver was decapitated during a dangerous stunt, the evidence leads the CSI’s to believe it was more than an accident. While gathering the evidence, the CSI’s find they must go into the world of “sideshows.”
A murder and kidnapping becomes personal when DNA from a crime scene reveals that Natalia’s sister Anya is one of the kidnapped women they are looking for. The team finds a safe full of photos of missing women and they must find the photographer who was using his camera to lure the unsuspecting women.
After a young woman is found dead shortly after she was auctioned off for charity, the team finds that the woman was trying to uncover the true nature of the event’s host. As the team delves deeper into the investigation they soon discover a larger plot that could put Miami in danger.
A Marine recruiter is found dead on a civilian shooting range with various bullet holes in him, but there is no blood at the scene. The investigators uncover that the victim was dead before he was shot and that his body was pulled onto the range. As the case advances, Horatio determines the murder may be tied to the death of a marine in Iraq who was killed in combat. Likewise, Natalia is shocked to learn that Nick asked Valera out and that she accepted.
When terror suspect Sonya Barak is targeted by her own people for assassination, she goes on the run, and Horatio sets out to capture her, both to protect her and bring her to justice.
After Nick is found to have been killed with all the evidence pointing to Natalia as the killer the rest of the team has been sidelined by the Internal Affairs investigation. Horatio with the help of the night shift lab and Calleigh’s ex-boyfriend have to find the evidence to clear Natalia.
After Frank steps on a land mine at a crime scene Horatio and the Bomb Technicians must deactivate the bomb. Delko gets hit with a large lawsuit after breaking up a domestic dispute.
A truck carrying weapons that were confiscated from previous crimes are now back on the streets of Miami. An old enemy of Horatio's puts the lives of two CSI's in harms way after a confiscated missile is launched into courthouse allowing Clavo Cruz to escape during his arraignment and injuring one CSI and the fatality of another CSI.
Horatio has Eric rushed to the hospital and watches as the doctors try to revive him. The rest of the CSI team finds evidence that may lead them to Cruz.
The CSIs investigate when the parents of a baby sitter in an upscale neighborhood are murdered. As the team sorts through the neighbors' secrets and lies, they find an unexpected love triangle as a motive for murder. Meanwhile, a key piece of evidence found at the crime scene leads Horatio to expose a doctor with some dirty secrets of his own.
Evidence suggests a victim may have been set up as bait, after he's found to have been attacked and killed by a black bear. It's discovered the killer may have been trying to hide another murder - that of a high priced hooker and her bodyguard, who were part of a prostitution ring catering to elite Miami clients.
After a wealthy businessman is killed at a charity event the CSI's first suspect his wife who was hosting the event. The blood evidence is thought to belong to the wife or her two secret twin sisters but leads the investigators in another direction after the victim is not who they thought he was.
After a scalped body is found near a Native American casino, Horatio believes that the owners of the Casino and the County Supervisor may have had some involvement in the murder.
After a movie star is killed at a celebrity rehab center, the CSI's investigate the secrets that the star was about to reveal and if this is what caused him to have been killed.
When the mistress involved with the husband in Miami's ugliest divorce battle is found to have been killed the divorce battle intensifies and the body count rises.
When one of Horatio's team lets their personal problems contaminate the investigation involving a spurned ex-lover, Horatio has to fire that team member.
After the murder of a suspected carjacker the team discovers that he may have been involved with a formidable drug lord and was suspected of drug running off Miami's shores.
There's a serial killer on the loose marking all of his victims with a Y on their chests and one or more of the csi's lives are in danger in this season 5 finale