Significant gender differences exist in the prevalence of substance use disorders in the United States. There is a trend among boys and girls aged 12 to 17 years toward comparable rates of use and initiation for alcohol, cocaine, heroin, and tobacco. If this trend continues, over time there may be a narrowing of the male-to-female prevalence ratios of substance abuse in the older age groups. This possibility is particularly disturbing because women have a heightened vulnerability to medical, physical, mental, and social consequences of substance use. Women also carry additional unique risks during pregnancy because of the effect on neonates. In addition, they have certain gender-specific cancer risks. Given this and the declining age of initiation of substance use in women, prevention and treatment efforts especially geared toward women (eg, education of all medical and paramedical staff, screening in primary care clinics, detection of drug use early in pregnancy or before conception, brief interventions and treatment programs that integrate women's needs) are exceedingly important to stop and ultimately reverse this growing trend.