Sherlock and Watson consult on a child abduction case involving a serial killer who is nicknamed "The Balloon Man," because he leaves a signature batch of balloons at each of his crime scenes.

Sherlock is reunited with “M.” a British criminal who appears to have followed Sherlock to New York. Meanwhile, Joan has reservations about leaving Sherlock and taking on a new client.

Business becomes personal for Sherlock when he is forced to partner with his estranged brother, Mycroft, to solve a case with life-or-death consequences.

When Holmes and Watson investigate a clown’s murder upstate, they discover a connection between his death and the creation of a new weaponized virus. Also, Watson helps Bell when he’s targeted by his new love interest Chantal’s ex-husband in attempt to sabotage her career at the district attorney’s office.

Season 5 ends with Holmes and Watson pursuing an elusive criminal as a gang war erupts in New York City. While the NYPD works to contain the violence, the two investigate the murder that appears to have ignited the city-wide conflict and discover that a familiar face is pulling the strings.

Holmes and Watson enter the world of rare antiquities when they investigate a case in which victim was killed during a Revolutionary War reenactment. Also, as Holmes grows frustrated with the length of his cognitive recovery, he finds solace in his growing friendship with Michael.