Substance use disorders (SUDs) are among the most common and costly conditions in veterans and active duty military personnel, adversely affecting their health and occupational and personal functioning. The pervasive burden of SUD has been a continuing concern for the Department of Veterans Affairs (VA) and Department of Defense (DoD), particularly as large numbers of service members return from Operations Enduring and Iraqi Freedom. The VA and DoD have prioritized implementation of evidence-based practices and treatment services to enhance the recognition and management of SUD in general medical and SUD specialty-care settings. This article summarizes the clinical practice guidelines for identifying, diagnosing, and treating SUD in VA and DoD general medical and SUD specialty-care settings, highlights evidence-based pharmacotherapy and psychosocial interventions for managing SUD, and describes barriers to successful treatment of veterans and service members at risk for SUD in VA and DoD health care systems.