Substance misuse is common among patients in primary care settings. Although it has a substantial health impact, physicians report low levels of preparedness to identify and assist patients with substance use disorders. An effective approach to office-based treatment includes a coherent framework for identifying and managing substance use disorders and specific strategies to promote behavior change. Brief validated screening tools allow rapid and efficient identification of problematic drug use, including prescription medication misuse. After a positive screening, a brief assessment should be performed to stratify patients into three categories: hazardous use, substance abuse, or substance dependence. Patients with hazardous use benefit from brief counseling by a physician. For patients with substance abuse, brief counseling is also indicated, with the addition of more intensive ongoing follow-up and reevaluation. In patients with substance dependence, best practices include a combination of counseling, referral to specialty treatment, and pharmacotherapy (e.g., drug tapering, naltrexone, buprenorphine, methadone). Comorbid mental illness and intimate partner violence are common in patients with substance use disorders. The use of a motivational rather than a confrontational communication style during screening, counseling, and treatment is important to improve patient outcomes.