We have summarized current knowledge regarding primary and secondary prevention of cardiovasular disease, with an emphasis on aspirin resistance and adverse effects. The use of combined therapy of aspirin and warfarin was discussed and the role of aspirin in patients with AF was reviewed according to the latest guidelines /Table 3/. The issue of primary prevention remains only partially resolved, though it would seem that male patients at moderate to high risk for CVD may benefit. On the other hand, the role of aspirin for secondary prevention in high risk populations and in ACS is well established. A dose of 75-150 mg/day has been validated in numerous studies with higher doses showing no additional effects. Aspirin should not be regarded as an innocent drug, since prolonged use in low risk populations carries the risk of serious adverse events, primarily bleeding. Adverse events seem to increase linearly with increased doses. Patient compliance remains a major issue regarding treatment failure and achieving clinical benefit and should be stressed at every physician-patient encounter. Further research is required to develop testing methods that are reliable, standardized and accurate for aspirin resistance, and currently such testing is not recommended. Withdrawal of aspirin treatment should not be considered an innocent act as it may cause susceptibility to atherothrombotic events.