We have reviewed the biochemistry of the normal and warfarinized vitamin K-dependent coagulation proteins, both individually and as members of their respective macromolecular enzyme complexes. Much has been learned in the past 10-15 years about the molecular mechanisms of coagulation. However, we have only scratched the surface and are beset by a number of interesting challenges. Clearly, we must begin to dissect the other vitamin K-dependent macromolecular enzyme complexes as has been done for prothrombinase. Prothrombin differs in fundamental ways from the other vitamin K-dependent proteins and we can anticipate significant differences as well as similarities in the other complexes. The presence of potentially functional domains in the non-catalytic portions of the vitamin K-dependent proteins and their similarities within this family of proteins should prove a fruitful area of future research. Finally, the evaluation of warfarinized vitamin K-dependent proteins, both in fundamental studies with purified systems and using uniquely engineered immunoassays, should shed light on basic molecular mechanisms and modes of monitoring warfarin therapy.