AbstractAttending physicians routinely encounter patients with signs and symptoms of anxiety and mood disorders as well as psychoactive substance use and psychoactive substance-induced organic mental disorders. These symptoms may represent either primary disorders or pathology that is secondary to other disorders. This article describes some of the relationships between substance use disorders and symptoms of anxiety and depressive disorders. In addition, some patients with these disorders may have a concurrent substance use disorder or be at high risk for developing one. Routine treatment of anxiety disorders with psychoactive drugs can be successful in many patients but may lead to iatrogenic dependence in high-risk patients. Prescribing for high-risk patients should include a stepwise treatment protocol having three progressive levels: (1) conservative, nonpharmacological approaches; (2) nonpsychoactive pharmacotherapy, including the use of anxioselective agents, such as buspirone; and (3) psychoactive pharmacotherapy, such as the use of benzodiazepines. Proper prescribing practices for high-risk patients are described in terms of diagnosis, dosage, duration, discontinuation, dependence, and documentation.