Platelet adhesion to the site of vascular damage is a critical early step in hemostasis. The platelet glycoprotein (GP) Ib-IX-V plays a key role in this step via its interaction with immobilized von Willebrand Factor (VWF). In addition to its well-known role in adhesion, GPIb-IX-V is critical for platelets' survival in circulation and plays an important role in the regulation of platelet clearance. Several mechanisms of platelet clearance work in concert to maintain a normal platelet count and ensure that circulating platelets are functionally viable via removal of senescent or activated platelets. Furthermore, dysregulation of platelet clearance underlies several bleeding disorders. GPIb-IX-V is central to many physiological mechanisms of platelet clearance including clearance via glycan receptors, clearance of VWF-platelet complexes, and fast clearance of transfused platelets. GPIb-IX-V dependent clearance also underlies thrombocytopenia in several bleeding disorders, including von Willebrand disease (VWD) and immune thrombocytopenia. This review will cover physiological and pathological mechanisms of platelet clearance, focusing on the role of GPIb-IX-V.