Buspirone, first synthesized in 1968 and marketed in 1986, is a pharmacologically unique azapirone drug. It is effective for treating generalized anxiety, but not other anxiety disorders. Buspirone also is efficacious for depression, either alone or together with an antidepressant drug, and for treating adverse sexual effects. Studies of buspirone for substance use disorders have had disappointing outcomes, although it may be useful for treating coexisting anxiety and one controlled study suggested efficacy for heroin detoxification. Buspirone may be considered a treatment option for managing irritability, agitation, and aggression in older adult patients with dementia as well as in pediatric patients, although additional effectiveness studies are warranted. Buspirone and melatonin may synergistically promote neurogenesis, supporting the potential use of this combination for treating depression and cognitive impairment.