This paper will bring a brief overview of the clinical aspects of psychotic depression, with emphasis in the differentiation between mood-congruent and mood-incongruent delusions. Biological aspects of this disorder will be reviewed. Changes have been found in serotonergic and dopaminergic neurotransmission and also a characteristic shortening of REM latency. Alterations of hypothalamic-pituitary-adrenal (HPA) axis are especially prominent and may have specific features in this disorder. Attention will be given to structural brain alterations, cognitive impairments and the relationships of both with the HPA alterations previously described. Finally, a treatment update will be provided. Combination of antidepressants and antipsychotics is still the preferred psychopharmacologic treatment. There is recent research in selective serotonin reuptake inhibitors as monotherapy, atypical antipsychotics and antiglucocorticoid strategies but more investigations are needed.