Depression is a common, but underdiagnosed and understudied problem in patients with renal disease. The overlap between symptoms of chronic medical illness and those of depression make for a particularly challenging diagnosis in this illness. The prevalence of depression varies with the diagnostic tool employed. The gold standard for the psychiatric diagnosis is the interview, using DSM-IV TR criteria. Researchers in the field of renal disease have often not distinguished between the diagnosis of major depression and high levels of depressive affect in studies. There are almost no data regarding the magnitude of depression in patients with chronic renal insufficiency, patients treated with peritoneal dialysis, and children with renal disease, compared with adults with end-stage renal disease treated with hemodialysis. The relationships between age, ethnicity, marital status and satisfaction, and perception of quality of life and level of depressive affect and diagnosis of depression, and medical outcomes have not been determined in patients with renal disease. The mediators which may underlie the deleterious effects of depression in patients with renal disease, and their relationship with stage of renal dysfunction have not been delineated. More emphasis must be placed on well-designed treatment studies and survival analyses in these populations, using longitudinal techniques.