Heparin therapy is gaining more use in many clinical conditions. Considering the serious nature of the diseases managed with heparin, it is necessary to achieve the therapeutic goal within a short time to gain the best possible benefit. Adequate anticoagulation also is necessary during procedures such as cardiopulmonary bypass and hemodialysis. Heparin resistance, inability to achieve therapeutic anticoagulation, has been described in as many as 22% of patients undergoing open-heart surgeries. The results of undercoagulation can vary from subclinical coagulation to death. It also is necessary not to over anticoagulate a patient and to understand the existence of alternative methods for monitoring heparin therapy to prevent excess heparin therapy and its complications. Many common dinical situations can induce resistance to the action of heparin. Being aware of the existence of heparin resistance and taking timely appropriate action would prevent catastrophic consequences. The use of antithrombin III is one way of preventing heparin resistance.