Ketamine is a U.S. Food and Drug Administration-approved anesthetic agent, which is increasingly being used “off label” for various psychiatric conditions. This session will educate practicing clinicians about the use of ketamine for psychiatric disorders, especially its use in treatment-resistant mood disorders and posttraumatic stress disorder. An overview of data from controlled research studies and experience in clinical practice settings will be presented. Important unresolved issues will be examined, including patient selection, treatment implementation (dose optimization, route of administration, maintenance treatment), and risk management, with the goal of providing a balanced view of a controversial “off-label” therapy.