Clinical depression is a common disorder with serious consequences. While it is treatable, a substantial proportion of patients do not respond to commonly used treatments. Ketamine was approved for use in the U.S. in 1970. It has traditionally been used for anesthesia. More recently, studies have found that ketamine can be a rapid-acting antidepressant. It is also possible that it can rapidly alleviate suicidal ideation. A single ketamine intravenous infusion can produce antidepressant effects within 4 hours. While traditional antidepressant medications have substantial efficacy, they require weeks for full effect and a substantial proportion of people do not fully respond. Though ketamine has not been approved for use as an antidepressant, the FDA approved a related medication, esketamine, in a nasal spray formulation, for use in treatment-resistant depression. Patients are considered treatment-resistant if they have major depressive disorder and, despite trying at least two antidepressant treatments at adequate doses for an adequate duration in the current episode, have not responded to treatment. Ketamine can produce euphoria and dissociation and has abuse potential. It has known side effects, including inducing psychotic episodes in at-risk individuals. The optimal dosing is unknown. The long-term side-effects, safety and effectiveness of esketamine are unknown.