Yi-gan san (YGS, yokukan-san in Japanese) was developed in 1555 by Xue Kai as a remedy for restlessness and agitation in children. Prompted by the increasing life expectancy of the Japanese population, geriatricians have begun to use this traditional regimen for behavioral and psychological symptoms of dementia in the elderly. Moreover, we reported that YGS therapy is a well-tolerated and effective remedy that improves the symptoms of borderline personality disorder and neuroleptics induced tardive dyskinesia. In a pilot investigation, we administered YGS as an open-label adjunct to antipsychotic medication to patients with treatment-resistant schizophrenia. The present review summarizes the available data supporting the clinical testing of YGS for psychiatric disorders. In addition, we extend our discussion to the potential applications of YGS for combining this treatment with cellular and molecular therapy.