Depressive symptoms are the most common psychological complication among patients with ESRD. Although depressive symptoms are a risk factor for increased morbidity and mortality, little is known about the mechanisms responsible for this association. Two pathways are described. The biological pathway involves interrelationships among depressive symptoms, inflammation, malnutrition, and atherosclerosis. The behavioral pathway includes the effects of depressive symptoms on dietary adherence. Recommendations include attention to therapeutic interventions that would influence these pathways to improve outcomes.