© 2007, Birkhäuser Boston. The mammalian hemostatic system has evolved to accomplish the task of sealing defects in the cardiovascular system. Hemostasis occurs in and around a disruption in a vascular conduit through which blood normally flows, and is characterized by the localized formation of thrombus. Consequently, the process of hemostasis is influenced by: (1) the biochemical properties of the cellular and soluble components of the hemostatic system, counterregulatory networks, and the vascular conduit; (2) the local hemodynamic conditions, which regulate the influx and efflux of substrates, cofactors, and catalysts, and which also impose loads on the forming clot; and (3) the local mechanical properties of the vasculature. We review the components of the hemostatic and negative regulatory systems and their biochemical functions, and the roles that local hemodynamics play in the regulation of hemostasis.