Alcohol and other drug abuse is increasingly recognized as a significant problem for women. Until recently, gender-specific research in substance abuse was woefully deficient. For many years, women were perceived as not suffering from substance abuse problems to the same extent as men. This perception, coupled with the intense social stigma associated with substance abuse, has created a situation in which women have been inadequately diagnosed, treated, and studied. Nonetheless, American women have begun closing the historic gender gap in drinking and using drugs. It has become clear that the motivations, patterns, and morbidity of substance abuse are different for women than for men. Women have distinct risk factors and reasons for beginning drug use. Female drug users are at high risk of acquiring and transmitting human immunodeficiency virus (HIV) to their social network via needle sharing, trading sex for drugs, sexual relations with steady partners, and perinatally and are expected to constitute half of all new patients with acquired immunodeficiency syndrome (AIDS) in the next decade. Finally, women exhibit different alcohol-related and drug-related symptoms and may require distinctive approaches to recovery. Because the substance abuse complications that bring women into medical care are primarily due to alcohol, opiate, and cocaine abuse, these three drugs are the focus of this article. The epidemiology, the life experiences associated with substance abuse, and clinical screening issues as well as physiology, clinical consequences, and treatment of substance-abusing women are reviewed. In each section, gender differences are highlighted where relevant.