Abstract： Major depressive disorder(MDD)is a mental disease characterized by persistent depression,lack of interest and impaired cognitive function.Antidepressants currently availablein clinic are effective but accompanied by many adverse reactions,such as slow onset,cognitive impairment,sexual dysfunction.Therefore,novel antidepressant targets and therapeutic strategies with rapid onset of action,cognitive enhancement and low adverse effects have increasingly become a promising sphere of research.Studies have suggested that Sigma-1 receptor plays an important role in combating depression by regulating inflammatory response,excitation/inhibition balance and endoplasmic reticulum homeostasis.Moreover,Sigma-1 receptor agonists may have the advantages of rapid onset,enhanced cognition and low adverse reactions,which show good prospects for the development of new antidepressants.This article reviews the research progress related to Sigma 1 receptors in the regulatory mechanism and treatments for depression in the hopes of providing new insights into new antidepressants.