Lipids and lipoproteins, as well as factors involved in hemostasis and thrombosis, play a central role in the pathogenesis of cardio- and cerebrovascular disease. In recent years it has become clear that a strong association exists between coagulation factors and plasma lipoproteins. Anionic phospholipids are necessary for the optimal activity of both pro- and anticoagulant enzymatic complexes. Cell membranes have traditionally been considered to provide the essential lipid-containing surfaces. However, in light of recent studies, plasma lipoproteins are also believed to provide appropriate surfaces to support coagulation. While triglyceride-rich lipoproteins and oxidized low-density lipoproteins are associated with a procoagulant profile, high-density lipoproteins (HDL) may have an anticoagulant effect. This paper reviews scientific data on the potential role of HDL as modulator of thrombotic processes.