Depressive disorders are 1.5–4 times more prevalent in medically ill patients than in the general population. Mood disorders can be regarded as the final common pathway developing from the interaction among multiple pathophysiological, psychological, and socioeconomic stressors that chronic illness imposes on the individual. Symptoms of clinical depression affect approximately 25% patients on hemodialysis and can be associated with low quality of life and increased mortality. The epidemiology of depressive disorders is less well studied in the renal transplant population. However, depression is a risk factor for poor outcomes, such as graft failure and death after renal transplantation. A high prevalence of severe psychological distress in patients with advanced CKD and its impact on CKD outcomes call for screening and intervention integrated in routine renal care. Preliminary data indicate that some of the selective serotonin reuptake inhibitor agents and time-limited, manualized, structured psychotherapies can be safe and effective for treating depression in this population.