The topic of mental health in female serial killers (FSKs) has been largely unexamined. It is plausible that many FSKs committed their crime before the introduction of standard diagnostic systems. The author’s team found that nearly 40% of FSKs in their study sample had a history of mental illness, including anxiety, depression, personality disorders, dissociative disorders, and factitious disorder imposed on another (FDIA), formerly called Munchausen syndrome by proxy (MSBP). This evidences that mental illness is overrepresented in FSKs compared to the population. Also in this chapter, the author reviews data on infrequent FSK mental health treatment, as well as on demeanor, sexual adjustment, and substance use. The author urges increased efforts for diagnosing and treating mental health issues to prevent murder. Case studies of FSKs Martha Woods and Marybeth Tinning illustrate mental health phenomena. The case of FSK Margie Barfield and a revisitation of the case of FSK Amy Archer-Gilligan illustrate substance abuse.