Disturbances of oxygen supply or cellular oxygen metabolism are common in critically ill patients. An understanding of dysoxia, or oxygen limited energy depletion, requires an understanding of the normal physiology of cell oxygen metabolism, and the compensatory mechanisms that supply high energy molecules under conditions of hypoxia. Understanding disorders associated with hyperlactataemia requires consideration of the cellular response in dysoxia, and pathology specific derangements in lactate metabolism. Much has recently been discovered about the causes of lactic acidosis in sepsis, and about the role of lactate in monitoring critically ill children. This review discusses how cells produce energy for metabolism under normal and hypoxic conditions; what happens to lactate produced during these processes; the clinical situations in which lactic acidosis has been described; the reasons why excess lactate may occur in sepsis; the evidence that a high lactate concentration is not simply a surrogate for tissue dysoxia; the relevance of lactate in the management of critically ill children; and suggested strategies to manage high blood lactate. Cells require oxygen for the production of ATP, the principal energy source. ATP is hydrolysed to ADP and high energy phosphate by adenosine triphosphatases in the cytosol.1 Energy released is used for the maintenance of membrane integrity, ionic pumps, and other specialised functions, such as contractility of muscle cells, and impulse transmission in neurons. The body’s stores of ATP will last no more than a few minutes, so it must be synthesised continuously as it is being used. Under physiological conditions, most ATP is generated from the metabolism of glucose, by the process of oxidative phosphorylation. The first stage of oxidative phosphorylation is the conversion of glucose to pyruvic acid; this occurs in the cytoplasm. The second stage, the oxidation of pyruvic acid, can only occur in the mitochondria as part of the …