This review points out the high morbidity and mortality associated with cardiovascular disease in patients with ESRD. Although there have been few randomized controlled trials that have examined this clinical problem in the population of patients with ESRD, there is a growing appreciation of the presentations and consequences of cardiovascular disease in this cohort. The etiology of this disease is multifactorial and the consequences include sudden death, coronary artery disease, and heart failure. The sudden death associated with ESRD has been linked to a progressive cardiac fibrosis that also accompanies left ventricular hypertrophy. Ischemic coronary disease is also common in this population. With regard to new therapy, efforts to control extracellular fluid volume and thereby control blood pressure are important. Two randomized trials have not shown the benefit of lowering low-density lipoprotein cholesterol concentrations in patients with ESRD, but such a strategy is thought to be beneficial in patients with chronic kidney disease. Efforts to optimally control calcium and phosphate concentrations are also beneficial, because vessel calcification remains a major problem for ESRD patients. The increase in vessel calcification leads to an increase in arterial stiffness and an increase in pulse wave velocity, which, in turn, increases cardiovascular morbidity and mortality. Additional recommendations are provided in this review including the use of erythrocyte stimulating agents, the cautious use of beta blockers with patients with a low ejection fraction systolic failure, and drugs that block the renin-angiotensin-alderosterone system.