Sherlock Holmes in the 21st Century is a unique Holmes and Watson story comprised of 3 parts. In Book One: Holmes steps into a strange fog shimmering in an alley just off Baker Street, little realizing the consequences of his curiosity. Watson naturally follows. It doesn't take them long to realize they're not in their own century anymore. Holmes is fascinated, Watson worried, but things start looking up when they come across lodgings for rent by none other than Wiona Hudson. They take that as a sign. When they are visited by Inspector Georgina Lestrade from Scotland Yard, a descendent of the Lestrade they know so well, Holmes starts to suspect that their arrival in the year 2000 was not a trick of nature. Before long they meet the head of British Intelligence who is none other than a clone of Mycroft called Morelock. The royal family is being terrorized by Moriarty's clone and only Holmes can stop him. Morelock is killed but is replaced by the next Mycroft clone in line, Myron.

Book Two: The Moriarty Gene. Unbeknownst to Holmes and Watson, they left behind a little something when they returned home. Those little somethings turn out to be Holmes' son, Sherlock Holmes Lestrade and Watson's daughter, Joan Watson Hudson, who use their cunning to trick Myron into showing them the time machine and explaining how it works. They break into the top secret facility and go back to 1892 to meet their fathers. Meantime back in 2022, a secret laboratory is discovered by the secret service and imperfect clones of Moriarty are found. The clones had been programed to clone themselves with unfortunate results. However, one clone less disabled than the rest invents a device that can piggyback off the time machine and transport him to the past to get new DNA from the original James Moriarty himself. Once again, Holmes is called upon to prevent a cloned Moriarty from wreaking havoc and to retrieve the piggyback device. This time he has the able assistance of his son and Watson's daughter as well as Watson.

Book Three: Mycrofts Galore. When the remaining three Mycroft clones in stasis are struck by lightning, they are activated and emerge from their chambers. When these clones learn they are to be terminated they steal the piggyback device and flee the century. Sherlock Junior discovers that their cells are in a state of flux, which affects their characters. It is up to them to track them down and either return them or terminate them, especially as one of the clones is kill crazy and has already killed Myron. Once again they return to the past and enlist Holmes and Watson's help in tracking them down, and this time even the original Mycroft gets involved with disastrous consequences.