This chapter addresses the scope of the problem of substance use among women and its etiology, risk, and protective factors; diagnostic criteria; symptoms; evaluation process and screening for differential diagnoses; use of diagnostic studies; treatment and management, including risk reduction; and future directions. As the field of substance use and care is evolving rapidly, the chapter focuses on providing the foundation for integrating new data and methods of care into practice as they become available. Substance use disorders occur when recurrent use of drugs and/or alcohol causes impairment, exemplified by health problems, disability, and failure to meet major responsibilities. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) guides the diagnosis of substance-use disorder, requiring that it be based on evidence of impaired control, social impairment, risky use, and pharmacological criteria. The symptoms related to the misuse of substances often co-occur with mental illness and commonly mimic psychiatric symptoms.