The energetic cost of ambulatory exercise is a significant contributor to the ability for humans to move about. There are generally accepted average values for the aerobic cost of walking and running, in terms of velocity, grade and the effect of air resistance. However, there is enough variation amongst humans for there to be both athletically and clinically important differences in the energetic cost of moving around. Studies from a variety of sources have demonstrated that practice with ambulation (particularly running) may have a meaningful effect on energetic cost, that the cost is related to the nature of weight distribution, including anthropometric characteristics of the individual, and that the energetic cost of moving may be influenced by both sub-clinical and clinical conditions. Despite earlier suggestions that systematic differences in the energetic cost of running was a primary contributor to the competitive success of runners of East African heritage, recent data do not support a uniquely “African” advantage in the cost of ambulation. Evaluation of the energetic cost of moving is also related to the method of evaluation. In running, the aerobic requirement of moving at fixed reference velocities as well as computations of the cost of running a certain distance may impact how the energetic cost of ambulation is appreciated. Lastly, although data about energetic cost is largely based on measured VO₂, there are strategies which can potentially account for non-oxidative ATP production.