A single infusion of ketamine has sustained antidepressant effects and significantly de-creases the risk of suicide,and the effects can last up for 7-10 days,but the underlying mechanism is un-clear. The mechanism was reviewed underlying the antidepressant effects of ketamine,and found that ket-amine may exert its antidepressant effect by regulating sleep/wake cycle,synaptic pruning,molecular path-ways,and neural circuits for treatment-refractory depression. Further studies are needed to investigate the ge-netic,molecular mechanisms underlying the sustained antidepressant effect of ketamine,and the associated imaging findings through in vivo imaging of animals and imaging genetics techniques,explore the optimal time for administration of ketamine,and then provide accurate scientific basis for enhancing its anti-depressant effect.