Compromising photographs and a case of blackmail threaten the very heart of the British establishment, but for Sherlock and John the game is on in more ways than one as they find themselves battling international terrorism, rogue CIA agents, and a secret conspiracy involving the British government.

A young man, Henry Knight, comes to Sherlock and John and asks them to investigate the case of his father's cuddle at the teeth of a gigantic hound. The case takes the duo to Dartmoor and a military base engaged in secret genetic experiments which may be connected to the passing of Henry's father.

Moriarty engineers three of the greatest crimes of the century, but then lets himself be caught. When the jury finds him not guilty on all charges and sets him free, Sherlock realizes that his nemesis is playing for bigger stakes, and that Sherlock's fall is Moriarty's ultimate goal.