Alcohol and drug use is a significant public health problem with particular implications for the health and safety of women. Women who abuse these substances are more likely to have untreated depression and anxiety and are at higher risk for intimate partner violence, homelessness, incarceration, infectious disease, and unplanned pregnancy. Substance abuse during pregnancy places both mother and fetus at risk for adverse perinatal outcomes. Data regarding the prevalence of substance abuse in women are conflicting and difficult to interpret. On the clinical level, strong arguments exist against routine urine drug testing and in favor of the use of validated instruments to screen women for drug and alcohol use both in primary women's health care and during pregnancy. A number of sex-specific screening tools are available for clinicians, some of which have also been validated for use during pregnancy. Given the risks associated with untreated substance abuse and dependence in women, the integration of drug and alcohol screening into daily clinical practice is imperative. This article reviews screening tools available to providers in both the prenatal and primary women's health care settings and addresses some of the challenges raised when women screen positive for drug and alcohol abuse.