Background: Depression occurs relatively commonly in people with chronic kidney disease (CKD), but it is uncertain whether depression is a risk factor for premature death in this population. Interventions to reduce mortality in CKD consistently have been ineffective and new strategies are needed. Study Design: Systematic review and meta-analysis of cohort studies. Setting & Population: Adults with CKD. Selection Criteria for Studies: Cohort studies identified in Ovid MEDLINE through week 3 December 2012 without language restriction. Predictor: Depression status as determined by physician diagnosis, clinical coding, or self-reported scales. Selection Criteria for Studies: All-cause and cardiovascular mortality. Outcomes were summarized as relative risks (RRs) with 95% CIs using random-effects meta-analysis. Results: 22 studies (83,381 participants) comprising 12,063 cases of depression (mean prevalence, 27.4%; 95% CI, 20.0%-36.3%) with a follow-up of 3 months to 6.5 years were included. Methodological quality generally was good or fair. Depression consistently increased the risk of death from any cause (RR, 1.59; 95% CI, 1.35-1.87), but had less certain effects on cardiovascular mortality (RR, 1.88; 95% CI, 0.84-4.19). Associations for mortality were similar regardless of the diagnostic method used for depression, but were weaker in analyses controlled for preexisting cardiovascular disease (RR, 1.36; 95% CI, 1.23-1.50). Limitations: Meta-analyses adjusting for antidepressant medication use were not possible, and data for kidney transplant recipients and individuals with earlier stages of CKD not treated with dialysis were limited. Conclusions: Depression is associated with a substantially increased risk of death in people with CKD. Effective treatment for depression in people with CKD may reduce mortality.