Selective serotonin reuptake inhibitors (SSRIs) have been widely used in clinical first-line treatment of depression. SSRIs exert their antidepressant effects by activating the 5-hydroxytryptamine (5-HT) receptors and regulating the release levels of 5-HT in the brain region. Whereas the chemical structures of SSRIs are different, resulting in the differences of metabolites in vivo and the adverse reactions caused by SSRIs. Adverse reactions such as gastrointestinal function, nervous system and sexual dysfunction caused by SSRIs are related to the five internal organs disorders of body’s. Traditional Chinese medicine believes that the treatment of diseases should be combined with treatment, eliminating diseases without damaging the body and restoring the physiological function of patients. As a classic prescription of traditional Chinese medicine, Xiaoyaosan has the effects of soothing liver and relieving depression, invigorating spleen and nourishing blood. Xiaoyaosan combined with SSRIs individualized medication can not only improve the antidepressant effect, but also reduce the adverse reactions caused by SSRIs. Therefore, according to the individual differences of patients with depression, Xiaoyaosan combined with suitable selective serotonin reuptake inhibitors was selected to treat depression. This article reviews the pharmacology of SSRIs, the efficacy of Xiaoyaosan and individualized medication in treating depression in recent years, providing a new perspective for the treatment of depression.