Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality in the western world. These disorders share a common pathophysiology -- atherosclerosis, which affects various arterial beds, leading to protean manifestations (coronary artery disease [CAD], stroke, peripheral arterial disease [PAD]). The platelet plays a pivotal role in the perpetuation and clinical expression of these disorders. The platelet, once believed to have a role confined to modulation of thrombosis and haemostasis, also plays an active role in vascular inflammation. Antiplatelet agents have become first-line therapy for CVD, and their unequivocal benefits are demonstrated in various basic and experimental models and supported by overwhelming evidence from clinical trials. Search is underway for more effective and safer antiplatelet therapy. Novel therapies are emerging to target the redundant pathways of platelet adhesion, activation and aggregation. Efforts are also ongoing to enhance implementation of existent therapy, target therapy selectively to high-risk patients and to those likely to respond (pharmacogenomics), and study the incremental benefits and safety of various antiplatelet combinations and their interaction with other medications in patients with CVD treated with polypharmacy.