Cardiac events are the major cause of death in hemodialysis patients. Because of the paucity of randomized clinical trials (RCTs) in hemodialysis patients, most cardiovascular therapies in this population are based on observational studies or results extrapolated from studies that excluded hemodialysis patients. However, associations discovered in observational studies do not prove causality, and these studies often report surrogate outcomes rather than clinical end points. Furthermore, interventions that show effectiveness in the general population may have drastically different outcomes and side effect profiles in hemodialysis patients. This review discusses the results of RCTs undertaken recently to evaluate cardiovascular therapies in hemodialysis patients and emphasizes clinically relevant outcomes. Although some interventions have produced similar outcomes in hemodialysis patients and the general population, others have not, suggesting that the management of cardiovascular disease in hemodialysis patients may require strategies that differ from the best practice guidelines applied to general population. Copyright © 2013 by the American Society of Nephrology.