Platelets play a major role in thromboembolic diseases, and so antiplatelet therapy remains crucial in treatment and prophylaxis. Upon vascular injury, platelets rapidly adhere to the exposed subendothelial matrix, after which they become activated, resulting in the recruitment of additional platelets from the circulation to eventually form a stable arterial platelet plug. Although controlled plug formation is desired for the prevention of excessive blood loss and for promoting wound healing, several pathological conditions may result in the formation of occlusive thrombi leading to severe clinical complications, including myocardial infarction and ischaemic stroke. Many antiplatelet approaches have been investigated, interfering with one or more of the different stages in thrombus formation. This review discusses antiplatelet agents that interfere with the three principal phases in thrombus formation: platelet adhesion, amplification of platelet activation and platelet aggregation. For each stage, novel experimental targets and clinically established antiplatelet strategies will be reviewed. Limitations and possible benefits will be discussed for each target.