Hemostatic control is based in a delicate balance between the activities of activator enzymes and their inhibitors, each one depending on a large number of proteins. Plasma Antithrombin III (ATIII) is one of the most important coagulation inhibitors and the fundamental enzyme for the therapeutical action of heparin. In the last years it was well established that ATIII deficiency accounts for a thrombotic state and inefficiency of heparin therapy. In this work, the authors review the biology of ATIII including its biochemical nature, its physiology, physiopathology and mechanism of action, analysing the implications of its deficiency. The authors draw the attention on clinical and laboratory studies that analyse the prevalence and importance of congenital and acquired deficiency of ATIII, in relation to the prevalence of venous thrombosis. Finally, the laboratory methods applied to the study of ATIII and to the biological control of heparin therapy are described with emphasis on the importance of the ATIII concentrates on this type of treatment. Also the fundamental aspects of heparin resistance are specially mentioned.