Muscular exercise requires transitions to and from metabolic rates often exceeding an order of magnitude above resting and places prodigious demands on the oxidative machinery and O-2-transport pathway. The science of kinetics seeks to characterize the dynamic profiles of the respiratory, cardiovascular, and muscular systems and their integration to resolve the essential control mechanisms of muscle energetics and oxidative function: a goal not feasible using the steady-state response. Essential features of the O-2 uptake (V O-2) kinetics response are highly conserved across the animal kingdom. For a given metabolic demand, fast. V O-2 kinetics mandates a smaller O-2 deficit, less substrate-level phosphorylation and high exercise tolerance. By the same token, slow. V O-2 kinetics incurs a high O-2 deficit, presents a greater challenge to homeostasis and presages poor exercise tolerance. Compelling evidence supports that, in healthy individuals walking, running, or cycling upright,. V O-2 kinetics control resides within the exercising muscle(s) and is therefore not dependent upon, or limited by, upstream O-2-transport systems. However, disease, aging, and other imposed constraints may redistribute. V O-2 kinetics control more proximally within the O-2-transport system. Greater understanding of. V O-2 kinetics control and, in particular, its relation to the plasticity of the O-2-transport/utilization system is considered important for improving the human condition, not just in athletic populations, but crucially for patients suffering from pathologically slowed. V O-2 kinetics as well as the burgeoning elderly population. (C) 2012 American Physiological Society. Compr Physiol 2:933-996, 2012.