In his biography of Sherlock Holmes, William S. Baring-Gould asserts that Challenger's mother was sister to Siger Holmes, the father of Sherlock. In Tarzan Alive, Philip José Farmer gives their relationship as cousins through Holmes's mother Violet and Challenger's father John Rutherford; Challenger's mother is stated to be a Scotswoman named Dorothy Swinton.
In the Conan Doyle stories, Challenger's wife is named Jessie, and they have a daughter named Enid, who marries Edward D. Malone. In Tarzan Alive, Challenger's wife is given as Enid Delgardie, and both are Wold Newton Family members. In his article The Challenging Rutherfords, Brad Mengel argues that there were actually two Challengers - George Edward Rutherford, and Edwin Rutherford, who collaborated on scientific papers under the alias of Edward Challenger until they went their separate ways, each taking the surname of Challenger. In Mr. Mengel's theory, George Edward Challenger married Jessie and had a daughter named Enid, and Edwin Challenger married Enid Delgardie. Mr. Mengel also sets out the two brothers' different careers, and details of their other children and descendents.
Tarzan Alive also suggests that Challenger might perhaps be the grandfather of Lew Archer; Mr. Mengel has identified reasons of chronology to rule that out, but has confirmed that Lew is Edwin Challenger's grandson instead.