Psychotic depression, although considered in DSM-IV to be a subtype of major depression, has many features of a separate disorder, including its own distinct phenomenology, epidemiology, family history, course of illness, biology and treatment. When evaluating patients with both depressive and psychotic symptoms, it is important to always consider psychotic depression as a possible diagnosis, as well as other diagnoses which may resemble it, such as bipolar disorder, schizoaffective disorder, schizophrenia with superimposed depression, delusional disorder and obsessive-compulsive disorder with poor insight and comorbid depression.Although patients with psychotic depression and those with depression without psychotic symptoms appear to respond equally well to electroconvulsive therapy (ECT), numerous studies have shown a significant lack of response to tricyclic antidepressants (TCAs) in the former group of patients compared with the latter. However, patients with psychotic depression appear to respond significantly better to combinations of antidepressants and antipsychotics. There is disagreement as to whether ECT is superior to combined TCA-antipsychotic treatment. Most researchers agree, however, that both are effective first-line treatments for psychotic depression. Amoxapine, selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) monotherapy, and combination treatment with an SSRI and an antipsychotic, are promising as possible additional first-line treatments. Atypical antipsychotics and the addition of lithium or other mood stabilisers to an antidepressant-antipsychotic regimen are potential treatments for patients with refractory psychotic depression.Psychotic depression is a recurrent disorder with a high rate of relapse after successful initial treatment with medications or ECT. The rate of relapse appears to be especially high when no maintenance therapy is used or when the antipsychotic drug of an antidepressant-antipsychotic combination is tapered off prematurely. Maintenance ECT is a promising tool for preventing relapse after initial ECT treatment.Additional studies of psychotic depression are needed to better determine the effectiveness of new treatments as well as to help resolve how to most effectively prevent relapse after acute treatment of this disorder.