Clinical evidence supporting the use of atypical antipsychotic medication (broad-spectrum psychotropic agents) in the treatment of depressive disorders is increasing rapidly. Animal models suggest that when atypical antipsychotic medications are used in combination with a selective serotonin reuptake inhibitor there is additional activation of frontal dopaminergic and noradrenergic neurotransmitter systems. This stimulated the initiation of several clinical trials that showed the efficacy of atypical antipsychotic medication augmentation of selective serotonin reuptake inhibitors for patients with treatment-resistant depression. There also are few case reports of successful treatment of depression with atypical antipsychotic medication alone. When a clinician is treating a depressed patient who did not achieve relief after trials with two different antidepressant regimens, one option to consider is augmentation with an atypical antipsychotic medication to ameliorate depressive symptoms.