Care of substance-using pregnant women is complex, difficult, and often demanding. Women's care providers must be aware of these women's unique psychologic and social needs and the related legal and ethical ramifications surrounding pregnancy. In addition, relating specific substances to perinatal outcome is difficult, because concurrent use of multiple substances is frequent and many pregnant abusers are members of economically disadvantaged segments of society in which unfavorable perinatal outcomes are more common. It is also difficult to follow up outcomes in such pregnancies prospectively and to analyze research data. This article discusses various issues related to pregnancies complicated by substance use, including perinatal pharmacology and teratogenic risks, identification of substance abuse, treatment approaches, and comprehensive perinatal management.