There is clinically important comorbidity between psychiatric and substance use disorders, particularly in women. Women with affective and anxiety disorders are more likely to present with alcohol or drug abuse/dependence. In turn, substance-abusing women are more likely to experience clinically significant depression and anxiety. Emerging evidence is pointing to an etiological role for anxiety disorders in the development of substance abuse/dependence; however, etiologic evidence is not as clear-cut for major depressive disorder. PTSD appears to be a particularly important factor for alcohol and drug dependence in women who have experienced childhood or adult sexual and or physical abuse. Although pharmacotherapy for affective or anxiety disorders is useful for ameliorating psychiatric symptoms, research is mixed on the effectiveness for improving alcohol- and drug-related outcomes. There is some limited evidence that women-specific services can improve treatment retention, substance use outcomes, and possibly psychosocial functioning compared with traditional mixed-gender programs. However, it is clear that women with co-occurring psychiatric and substance use problems are challenging to engage and retain in care. Physicians providing women's reproductive health services can serve a vital role in the identification and referral of substance-abusing women. Particular attention should be focused on screening and assessment of alcohol and drug use and problem severity among women who have identified psychiatric disorders or who are receiving antidepressant or anxiolytic medications. Recognition and referral for both psychiatric and substance use disorders are critical for long-term health and psychosocial improvement.