Cardiovascular (CV) disease in uremic patients is a major concern to the nephrologist because it represents the main cause of morbidity and mortality in chronic renal failure patients, both predialysis and while on dialysis therapy. CV mortality is 3 to 20 times higher in dialysis patients than in the general population at similar age. Of note, a high prevalence of CV comorbidity is already present at start of maintenance dialysis, and is predictive of subsequent mortality on dialysis. CV disease progresses over years prior to the onset of ESRD, because risk factors develop from the early stage of chronic renal insufficiency. However, CV disease may be prevented or attenuated in patients who benefit from early, regular care of CV risk factors. Mechanisms of uremic cardiopathy, the major cause of mortality in uremic patients, are multifactorial and their effects are cumulative. Risk factors for left ventricular hypertrophy are hypertension, anemia, fluid overload and arteriosclosis, all of which are amendable by therapy. Risk factors for accelerated atherosclerosis, responsible for ischemic cardiopathy and myocardial infarction, are both common factors (e.g., hypertension, tobacco smoking and diabetes) and factors more specific for the uremic state (e.g., dyslipidemia, hyperhomocysteinemia and oxidative stress), all of which also are amendable by proper therapy. As a result, mixed hypertensive and ischemic cardiomyopathy develops, ultimately leading to cardiac failure, together with accidents resulting from valvular and arterial calcifications (favored by calcium-phosphate disorders), and from occlusion of coronary, cerebral and peripheral arteries. Cardioprotective therapy thus has become a cornerstone in the management of chronic renal failure patients, in conjunction with renoprotective therapy. Cardioprotective strategy involves optimal treatment of hypertension, anemia, fluid overload, dyslipidemia, hyperhomocysteinemia and calcium-phosphate disorders, and smoking cessation. To achieve a maximal efficacy, such treatment has to be initiated as early as possible in the course of renal failure. Because of its complexity, the integrated combined nephrotective and cardioprotective therapy requires early and sustained guidance by a nephrologist throughout the whole predialysis period.