Atherosclerotic cardiovascular disease is a significant cause of morbidity and mortality in patients with chronic renal failure. It is unclear, however, if atherosclerosis in fact occurs at a higher incidence compared with the nonuremic population matched for age, hypertension, and diabetes mellitus or if it occurs at an accelerated rate following the onset of end-stage renal disease. The extent of true atherosclerotic lesions, versus clinically diagnosed “atherosclerosis,” in patients with chronic renal failure is equally unclear. Potentially, the uremic state per se, the dialysis treatment, and factors unrelated to renal failure may participate in atherogenesis. The relative contribution of each of these factors is unknown. In this review, we discuss the pathology of “atherosclerotic” lesions in patients with chronic renal failure and the putative factors involved in atherogenesis in this population and describe the results of available studies examining the issue of accelerated atherosclerosis in uremia.