Substance abuse poses significant health risks to childbearing-aged women in the United States and, for those who become pregnant, to their children. Alcohol is the most prevalent substance consumed by childbearing-aged women, followed by tobacco, and a variety of illicit drugs. Substance use in the preconception period predicts substance use during the prenatal period. Evidence-based methods for screening and intervening on harmful consumption patterns of these substances have been developed and are recommended for use in primary care settings for women who are pregnant, planning a pregnancy, or at risk for becoming pregnant. This report describes the scope of substance abuse in the target population and provides recommendations from the Clinical Working Group of the Select Panel on Preconception Care, Centers for Disease Control and Prevention, for addressing alcohol, tobacco, and illicit drug use among childbearing-aged women.