Depression is a mental disorder with a high prevalence rate， a high recurrence rate， and a high suicide rate. At present， it has become a major public health problem the world faced. 15 % -20 % of major depression can develop into treatment resistant depression. However， at present， traditional antidepressants often take 2 to 3 weeks to gradually take effect. Delayed effects can lead to increased risk of suicide and selfinjury in patients. Ketamine is a commonly used general anesthetic in the clinic. Since the early 1990s， it has been found that it has a definite antidepressant effect and can rapidly improve the symptoms of severe and treatment resistant depression. However， due to the restrictions on the clinical use of narcotic drugs and other problems such as substance abuse， the clinical promotion of narcotic drugs is affected. In recent years， ketamine in the treatment resistant depression has become a hot topic in academic circles. This article reviews the mechanism， research status and safety of ketamine in treatment resistant depression.