Although the pathophysiology of depression has not been clearly elucidated yet, the mTOR (mechanistic target of rapamycin) signaling pathway has recently taken an increasingly important position in the pathophysiology of depression. In this review, preclinical and clinical studies of depression related to the mTOR signaling pathway will be summarized to explore the current position of mTOR in depression. Because the role of mTOR in the mechanism of the antidepressant effect of ketamine has been attracting attention, related studies will also be reviewed. Summarizing these studies, this review would like to suggest the basis and future direction for treatment and research of depression.