Objectives: The aim of this systematic review was to study the benefits and risks of beta-adrenergic antagonists (beta-blockers) in patients with chronic kidney disease (CKD). Background: There is an excess burden of cardiovascular disease and death in people with CKD. Despite their potential benefits, the effects of beta-blockers in this population are uncertain. Methods: CENTRAL (Cochrane Central Register of Controlled Trials), Medline (Medical Literature Analysis and Retrieval System Online), and Embase (Excerpta Medical Database) were searched for randomized controlled trials with at least 3 months of follow-up in patients with CKD stages 3 to 5 that reported mortality outcomes. Summary estimates of effect were obtained using a random effects model. Results: Eight trials met criteria for review: 6 placebo-controlled trials involving 5,972 participants with chronic systolic heart failure and 2 angiotensin-converting enzyme inhibitorcomparator trials involving 977 participants not known to have heart failure. In CKD patients with heart failure, compared with placebo, beta-blocker treatment reduced the risk of all-cause (risk ratio [RR]: 0.72, 95% confidence interval [CI]: 0.64 to 0.80) and cardiovascular mortality (RR: 0.66, 95% CI: 0.49 to 0.89), but increased the risk of bradycardia (RR: 4.92, 95% CI: 3.20 to 7.55) and hypotension (RR: 5.08, 95% CI: 3.48 to 7.41). Quantitative meta-analysis was not performed for the nonheart failure studies due to substantial clinical diversity or lack of informative data. Conclusions: Treatment with beta-blockers improved all-cause mortality in patients with CKD and chronic systolic heart failure. There is insufficient evidence to conclude whether people with CKD who are not known to have heart failure derive benefit from beta-blockers.