Depression is the most frequent psychiatric problem in patients with chronic renal disease and may predict patient outcome and mortality. Depression is linked to stressful life characterized by many losses and by dependence, which even may lead to suicide. Despite the large number of patients with chronic kidney disease and the economic burden they represent, only a few of these patients receive adequate diagnosis and therapy. Diagnostic and Statistical Manual of Mental Disorders-IV criteria for major depression may help in differentiating symptoms of uremia and depression. Pharmacotherapy is available and antidepressants (tricyclic antidepressants and selective serotonin re-uptake inhibitors) have been used successfully in various studies. Finally, there is a need for further well-designed, longitudinal, survival studies to clarify the relationship better between depression and the different stages of renal dysfunction.