The burden of cardiovascular disease is high in patients with chronic kidney disease or end-stage renal disease. The presence of kidney dysfunction affects the cardiovascular system in multiple ways, including accelerated progression of atherosclerosis and valvular disease, the exacerbation of congestive heart failure, and the development of pericardial disease. This comorbidity results not only from the concordance of shared risk factors, but also from other issues specific to this population, such as systemic inflammation and vascular calcification. Furthermore, both the sensitivity and specificity of noninvasive testing modalities, and the efficacy of several pharmacotherapeutic strategies, are diminished in this population. The exclusion of patients with severe kidney disease from many clinical trials of cardiac interventions raises various therapeutic uncertainties, and kidney disease itself is likely to alter the underlying cardiovascular physiology. In this Review, we discuss aspects of the epidemiology, pathophysiology, and diagnosis of cardiovascular disease in patients with kidney disease, and propose specific, evidence-based recommendations for pharmacological and surgical treatment.