Coronary blood flow is tightly adjusted to the oxygen requirements of the myocardium. The underlying control mechanisms keep coronary venous pO ₂ at a rather constant level around 20mm Hg under a variety of physiological conditions. Because coronary flow may increase more than 5-fold during exercise without any signs of under- or overperfusion, coronary flow must be controlled, at least in part, in a feed forward manner. Likely metabolic factors contributing to feed forward control are carbon dioxide and reactive oxygen species. Adaptation of coronary flow to exercise under physiological conditions involves in addition to metabolic control feed forward neuronal and endothelium-dependent control. Under pathological conditions, e.g. vessel stenosis or anemia, or specific environmental conditions, e.g. high altitude exposure, cardiac oxygenation may become critical, especially if oxygen demand is increased during physical exercise. Under such conditions the fall of coronary pO ₂ may directly result in opening of oxygen sensitive potassium or closure of calcium channels. Furthermore the fall of pO ₂ results in the production of vasoactive metabolites, e.g. adenosine, nitric oxide or prostaglandins, and in proton accumulation. All of these adaptations support a reduction of coronary vessel resistance. This article is part of a Special Issue entitled "Coronoray Blood Flow".