Platelet adhesion mediated by adhesion receptors plays critical roles in hemostasis and thrombosis and in other conditions such as inflammation, tumor metastasis and growth, and host defense. A platelet adhesion receptor selective for an adhesive ligand often synergizes with adhesion receptors selective for other adhesive ligands to overcome flow shear force and stabilize adhesion. Platelet adhesion receptors transmit signals that converge into the platelet activation signaling networks to induce platelets responses including aggregation of platelets, secretion of pro-thrombotic, pro-inflammatory and growth factors, expression or release of pro-coagulant molecules and vesicles, and retraction of clot. Most current anti-platelet drugs works by inhibiting ligand binding function or the activation of ligand binding function of platelet adhesion receptors. This chapter focuses on the integrated roles of platelet adhesion receptor in platelet adhesion and thrombus formation, their regulation and signaling mechanisms, which are important for the physiological and pathophysiological roles of platelets.