In 1992, a comprehensive review of all previous studies comparing patients suffering from psychotic major depression (PMD) to non-PMD patients was published. In this review we present data of all studies comparing PMD patients to non-PMD published in the English language after 1992. The research papers reviewed have shown the following general profile of PMD: the point prevalence of PMD is about 0.4% and 19% of patients with a major depressive episode had psychotic symptoms as well. PMD was found to be a more severe form of depression with more feelings of guilt and more pronounced psychomotor disturbance. Additionally, PMD patients compared to non-PMD were found to be more severely impaired in the cognitive domains of attention, psychomotor speed, executive function and memory, regardless of depressions severity. As regards to the prognosis of the disorder, PMD is associated with poorer short-term outcome; nevertheless, in the long-term period ( > 2-5 years) the prognostic significance of delusions in major depression tends to become weaker. However, the recurrence of psychotic episodes in PMD patients suggests that PMD runs “true to form”. Of note, young PMD patients with acute onset of the disorder are at greater risk to develop bipolar disorder. Furthermore, PMD was associated with greater HPA abnormalities, higher plasma cortizol levels during the afternoon, lower serum D H activity than age-matched non-PMD patients and healthy controls. In addition, more brain atrophy and paralimbic abnormalities may play a crucial role in the delusion formation. With respect to management of PMD, starting with a combination of AD plus AP or AD as monotherapy may be preferred. Nevertheless, methodological problems in studies on SSRIs as monotherapy and according to recent data -favoring the combination over AD monotherapy- the AP plus AD treatment regime takes precedence.