Patients affected by cardiovascular disease (CVD) are treated with antiplatelet agents (AA) and/or anticoagulant drugs, which are fundamental in the management of stroke, coronary atherosclerotic disease, peripheral vascular disease and atrial fibrillation. CVD is the most important cause of death in chronic renal failure (CRF). Death rates from myocardial infarction (MI) and from all other cardiac causes exceed those for the general population. Incidence of MI in CRF is triple that in the general population. Moreover, mortality is seven- to eight-fold higher in patients requiring chronic hemodialysis compared to the general population, and approximately 40% of deaths in this population are attributable to coronary artery disease (CAD). For these reasons, AA are widely used in patients affected by CRF. Current data do not support a protective effect of antiplatelet administration in hemodialytic patients as primary prevention of cardiovascular mortality. Different results have been obtained concerning secondary prevention of CVD. The Cooperative Cardiovascular Project demonstrated that dialysis patients treated with aspirin following MI had a 43% lower mortality. Another study reported that the use of aspirin and beta-blockers following MI was associated with lower mortality in CRF patients. However, aspirin plus clopidogrel seems to increase the hemorrhagic risk without a significant reduction in cardiovascular mortality and there are insufficient data to support the use of new AA drugs in hemodialytic patients. In conclusion, since CRF patients are one of the groups at highest risk for atherosclerotic events, it could be reasonable to use aspirin in HD patients. However, the bleeding risk in HD patients needs to be strongly evaluated, especially before starting dual AA treatment.