In this review, we presume that the process of thrombus formation, as assessed in whole blood flow studies and in experimental (murine) thrombosis studies, reflects the platelet responses in human hemostasis and thrombosis. Following this concept, we give an up-to-date overview of the main platelet receptors and signaling pathways that contribute to thrombus formation and are used as targets in (pre)clinical intervention studies to prevent cardiovascular disease. Discussed are receptors for thrombin, thromboxane, ADP, ATP, prostaglandins, von Willebrand factor, collagen, CLEC-2 ligand, fibrinogen and laminin. Sketched are the consequences of receptor deficiency or blockage for hemostasis and thrombosis in mouse and man. Recording of bleeding due to (congenital) platelet dysfunction or (acquired) antiplatelet treatment occurs according to different protocols, while similar laboratory methods are used to determine platelet function.