The major clinical importance of plasma protein C is attested to by the strong association between inherited protein C deficiencies of half normal levels and recurrent venous thromboembolic disease. Homozygous protein C deficient individuals do not survive beyond infancy without continuous therapeutic intervention. The spectrum of protein C deficiency is becoming broader and includes patients with both abnormal molecules and half normal levels of functionally active molecules. Rarely, a few young adults with thrombosis have been identified with protein C levels below 25%. Studies of protein C activity have been hampered until the very recent developments of functional assays of plasma protein C. Application of these assays to a wide variety of clinical situations involving thrombotic complications is just beginning and may lead to an explosive proliferation of new data that should prove most fascinating and give much further insight into the contributions of protein C in the regulation of thrombosis.