Abstract: The etiology and pathogenesis of depression is complex, the regulation of serotonin signaling pathway is one of the most important mechanisms for commercially available antidepressants. In addition to serotonin transporter, recent studies have shown many other serotonin receptor subtypes also play an important role in the treatment of depression, which has become one of the hot topics of antidepressants. Therefore, the progress of serotonin receptors and new structure with the activity of regulating serotonin receptors as well as part of the structure-activity relationships are reviewed in this paper in order to provide reference for the further research and development of antidepressants.