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It is well recognized that depression represents a significant co-morbidity for patients already confronted with chronic medical conditions. Individuals with kidney disease are not an exception to this observation. Many potential psychological, social, and biological contributions to the high rate of depression in patients with end-stage renal disease (ESRD) have been identified. Patients with ESRD on dialysis often suffer the loss of work status and time, health, and independence. Approximately one in four patients with ESRD chooses to voluntarily discontinue dialysis treatment. Many different classes of antidepressants have been used in this complex patient population. The medications most often utilized include the selective serotonin reuptake inhibitors (SSRIs) and the serotonin-norepinephrine reuptake inhibitors (SNRIs). The administration of tricyclic antidepressants (TCAs) in patients with renal disease is rife with potential complications. Electroconvulsive therapy has been used in patients with ESRD, and it appears well tolerated and effective in this patient population.