Many changes in the vasculature, hemostasis and endothelium, including alterations of platelets, coagulation and fibrinolytic factors, occur during aging. While the increasing hypercoagulability observed with aging may account for the higher incidence of thrombotic cardiovascular disorders in the elderly, the lack of genetic protective factors against thrombosis in healthy centenarians suggests that little is yet known about the age-associated changes of hemostasis. The complex inter-relationships between inherited and acquired factors influencing the hemostatic system during aging are discussed in this review.