Since the introduction of cardiopulmonary bypass, clinicians have tried to define the optimal blood flow for a given patient. The difficulty in determining a correct blood flow lies in the fact that cardiac surgery is done in a very inhomogeneous population, from neonates to the octogenarian, and often under non-physiologic conditions (hypothermia, hemodilution, low flow, etc.). Although clinicians acknowledge that maintaining a minimum oxygen delivery is more meaningful than using a fixed flow rate based on the metabolic needs of awake resting volunteers, the latter is most used in clinical practice. This is explained by the fact that no values are available on critical oxygen delivery for adequate tissue oxygenation under a given clinical condition. This was an overview of the relevant literature. In most centers, perfusionists use in-line monitoring, such as venous saturation or venous blood gases, for estimation of adequacy of tissue perfusion. Unfortunately, these oxygen-derived parameters have a poor correlation with anaerobic energy supply. Measurement of intermittent whole blood lactate concentration is used to compensate for this poor relationship, but as it monitors the concentration at given time points, it precludes optimally timely intervention by the perfusionist. The physiologic buffering by bicarbonate of the acid generated by converting pyruvate into lactate will produce carbon dioxide. As a consequence, carbon dioxide-derived parameters do have a good correlation with inadequate tissue perfusion. In-line monitoring of carbon dioxide production gives real-time information on tissue perfusion. Use of a standard reference flow for each patient is a poor option, because it does not reflect the metabolic need of the patient. Oxygen-derived parameters, such as venous saturation or partial venous oxygen tension, are poor predictors of anaerobic metabolism. A combination of intermittent whole blood lactate measurement with carbon dioxide-derived parameters predicts anaerobic energy production and allows proactive intervention by the perfusionist.