Hemostasis at sites of blood vessel injury and its pathologic counterpart, thrombosis, involve a complex interplay between several blood elements: soluble proteins of the blood coagulation system, blood cells (most prominently platelets) and cell fragments, and elements of the vessel wall (endothelial cells and, at sites of injury, the exposed matrix and deeper cellular components). In this review, we focus on ways in which specialized membrane microdomains known as lipid rafts are involved in various phases of hemostasis and thrombosis.