Thromboembolic disease is a major complication of protein C (PC) deficiency, which is among the increasing number of recognized causes of hereditary thrombotic disease. The laboratory evaluation of PC is of the utmost importance in the accurate diagnosis of this deficiency. In this review, we describe the various types of clinical antigenic and activity assays of PC. The attributes of each type of assay are discussed, as well as the value of each assay in diagnosing the various acquired and hereditary deficiencies of PC. This basic review is intended for laboratories planning to institute PC assays.