The central mystery revolves around the ancient curse of the Baskervilles, a legend of a fearsome, supernatural hound that supposedly hunts down members of the family. Sherlock Holmes and Dr. Watson investigate the recent death of Sir Charles Baskerville and the threat to his heir, Sir Henry, to determine if the curse is real or if a human hand is behind the tragedies.

The primary investigators are the brilliant consulting detective Sherlock Holmes and his chronicler, Dr. John Watson. While Holmes initially sends Watson to Dartmoor to gather information, he eventually joins the investigation himself, bringing his unparalleled deductive skills to bear on the complex case.

This novel is highly significant because it marked Sherlock Holmes's triumphant return after his presumed death in "The Final Problem," much to the delight of his readers. Its compelling plot, atmospheric setting, and classic confrontation between Holmes's intellect and a seemingly supernatural threat have cemented its status as one of the most famous and beloved detective stories ever written, often ranked as the best of the four Holmes novels.