This article reviews past approaches to heparin and protamine dosing and summarizes current practice. The author elucidates his experience with the Celite activated coagulation time (ACT), with attention to his adoption of a value of 400 seconds for this time; the adoption of an ACT of 480 seconds by Bull et al (J Thorac Cardiovasc Surg 69:674-684, 1975) and Young et al (Ann Thorac Surg 26:231-240, 1978); the proposed use of heparin response curves by Bull et al; the author's experience with a unitized dosing system to individualize dosing of heparin; and the use for this purpose by Despotis et al (J Thorac Cardiovasc Surg 110:46-54, 1995) of a system based on protamine titration. In more than 270 adult cardiac surgery patients, the unitized dosing system identified patients with high sensitivity or resistance to heparin and facilitated exact individualized doses to be given to produce the desired effect. Thus, less heparin was used in short bypass runs. Patients received less protamine than they would have with any other formula, and there was less blood loss and fewer transfusions required. Currently, no claims for efficacy or safety can be made for maintaining heparin concentrations greater than 3 U/mL. Pending further clarification, heparin dosage cannot be safely reduced when using heparin-bonded circuits. Aprotinin is not a procoagulant during cardiopulmonary bypass. Emerging studies suggest that graft patency is not affected by aprotinin use. The Celite ACT should not be used to monitor heparin effect and safety when using aprotinin; the kaolin ACT should be used instead.