Substance use disorder (SUD) is among the leading causes of premature morbidity and mortality and imposes significant health, economic, and social burdens. Gender differences have been found in the development, course, and treatment of SUD, with women at increased risk for physiologic and psychosocial consequences compared with men. Reasons for these differences are multifold and include biological, genetic, environmental, and behavioral factors. This article discusses SUD among women, emphasizing clinical considerations for care. Specific topics include epidemiology, sex and gender differences, common comorbidities, screening, diagnosis, treatment, pregnancy, and sociocultural factors.