Depression is common in patients with end-stage renal disease and has been linked to increased mortality. Screening for depression in the general medical population remains controversial; however, given the high prevalence of depression and its significant impact on morbidity and mortality, a strong case for depression screening in patients with end-stage renal disease can be made. Several studies have been performed to validate the more common depression screening measures in patients with chronic kidney disease. The Beck Depression Inventory, the Hamilton Rating Scale for Depression, the Nine-Question Patient Health Questionnaire, and the Center for Epidemiologic Studies Depression Scale are some of the measures that have been used to screen for depression in patients with end-stage renal disease. Data suggest a higher Beck Depression Inventory cutoff score, of >14 to 16, will have increased positive predictive value at diagnosing depression in patients with end-stage renal disease. There are limited data on the treatment of depression in this patient population. Pharmacotherapy, including selective serotonin reuptake inhibitors, can be used if deemed clinically indicated, and no active contraindication exists. There are even fewer data to support the role of cognitive behavioral therapy, social support group interventions, and electroconvulsive therapy for treatment of depression in patients with chronic kidney disease. Larger randomized, controlled clinical trials aimed at the treatment of depression in patients with end-stage renal disease are desperately needed.