HIV is an increasingly critical and costly health problem for American women. Substance use plays a major role in HIV infection in women. There are several plausible explanations for the association between substance use and HIV risk behavior. Pregnant substance abusers are a population deserving of special attention given the prevalence of risk behavior in this population and the added risk of perinatal transmission of HIV. Current guidelines for the screening and treatment of HIV among pregnant women and their infants are delineated. Substance abuse treatment has a limited impact on HIV risk behavior in female substance abusers. Similarly, traditional knowledge- and skill-based HIV risk reduction interventions have modest efficacy in this population. Hence, there is a need to develop new interventions that directly target sex- and drug-related HIV risk behavior among female substance abusers. Recent work suggests that the incorporation of motivational interviewing components into traditional HIV risk reduction interventions may be a promising new direction for the field.