Sherlock Holmes, fresh out of rehab, is teamed with a sobriety partner, a former surgeon named Watson. They have to learn to work together even as they tackle their first case, the mysterious death of a doctor's wife.

Two heirs of a fortune are murder suspects, but one sister has an undeniable alibi and the other is a coma patient. Holmes is baffled as to how a coma patient could be the killer until another addict in his support group gives him an idea.

Holmes is hired by a Wall Street firm to find a missing executive. He finds the man, murdered, and then detects a pattern of mysterious deaths throughout the company's branches. But who could be benefiting from all of the murders?

During a visit to a hospital's morgue to do some experiments, Holmes deduces that a terminally ill patient has been murdered. Is this an isolated incident or is there an "Angel of Death" operating in the hospital?

After a small jet crashes killing four people, Holmes battles both the police and the NTSB when he believes one of them was murdered before the crash occurred. Meanwhile, Watson confronts Holmes over a past friend, someone named Irene.

While Watson struggles with Holmes over finding a new sponsor, they work a case of a bombing of an Internet company. The bomb was planted four years ago but it's inconceivable that anyone would plan a bombing so far into the future.

The manager of a high-end hotel that caters to diplomatic VIPs is found dead in the hotel's laundry. After first suspecting a connection to a prostitution ring, Holmes believes the answer lies in her treacherous past.

Holmes discovers a man running an internet conspiracy site is dead. As he follows the chain of clues, he becomes aware of the "Red Team" and the trail leads him further down the rabbit hole than he ever imagined.

A convicted killer who is supposed to donate a kidney to his sister ends up killing the surgical staff before escaping. Holmes is forced to work with a profiler (whom he can't stand) because she supposedly can predict what he will do next.

Holmes' former drug supplier comes to him for help to find his kidnapped daughter. He agrees to help him despite Watson's protests. When Holmes appears stymied, the former dealer encourages Holmes to go back on drugs, hoping it will help him solve the case.

A wealthy scientist comes to Holmes with a unique case: he believes he has been "poisoned" with a genetic disorder. Holmes has to determine how a healthy person can be contaminated with a genetic disease that no one in his family has.

Watson works a case on her own about a woman who has disappeared while Holmes deals with a subway murder. As they work their separate cases they gradually appear to be connected, even though they can't determine exactly how.

In the middle of a winter storm, Holmes and Watson must solve the murder of a guard during a botched robbery and unravel the killer's true plan. The pair also get an interesting new roommate.

A blackmailer uses tapes of underage girls to get money from their fathers. When Holmes witnesses the blackmailer's murder, it becomes a race to find out who his accomplice is and prevent the videos from being released on the Internet.

A man connected to the classification of a valuable building as a landmark trust dies when his pacemaker is deliberately short circuited. Holmes soon learns the one behind the murder is an old nemesis known to him only as "Moriarty".

Moriarty asks Holmes to find out who murdered a mechanic in Brooklyn. Despite Watson's protests, Holmes thinks this case will help him uncover Moriarty's true identity, but it will, in fact, lead Holmes to something much worse.

Holmes reconnects with Irene, his one true love that he thought had been taken from him by Moriarity. He tries to protect her as she recovers from her trauma but he soon learns that it isn't she that needs protection.

While recovering from his gun shot wounds, Holmes eschews painkillers while working on a case of a Greek shipping magnate - involving an assassination and currency manipulation - before his final showdown with Moriarty.