Approximately one-third of patients with depressive develop to treatment-resistant depression （TRD） since they do not respond to existing antidepressants. TRD is a chronic depressive state with a long course of illness， which is highly resistant to current treatment regimens and has poor prognosis， putting a heavy burden on the patient's family and society. This review summarizes the current treatment options for TRD， reviews and analyses the evidence for the use of ketamine in TRD，focusing on clinical routes of administration， dose， and duration of efficacy. Furthermore， ethical factors were added to the safety discussion of ketamine， hoping to provide a reference for the clinical treatment of TRD and the standard use of ketamine.