The coagulation system is part of the continuum of host response to injury and is thus intimately involved with the kinin, complement and fibrinolytic systems. In fact, as these multiple interrelationships have unfolded, it has become difficult to define components as belonging to just one system. With this limitation in mind, an attempt has been made to present the biochemistry and physiology of those factors which appear to have a dominant role in the coagulation system. Coagulation proteins in general are single chain glycoprotein molecules. The reactions which lead to their activation are usually dependent on the presence of an appropriate surface, which often is a phospholipid micelle. Large molecular weight cofactors are bound to the surface, frequently by calcium, and act to induce a favorable conformational change in the reacting molecules. These molecules are typically serine proteases which remove small peptides from the clotting factors, converting the single chain species to two chain molecules with active site exposed. The sequence of activation is defined by the enzymes and substrates involved and eventuates in fibrin formation. Multiple alternative pathways and control mechanisms exist throughout the normal sequence to limit coagulation to the area of injury and to prevent interference with the systemic circulation.