There are many ways to measure physical functioning. Oxygen uptake at peak exercise is considered to be the most objective or 'gold-standard' measure and is determined by the integrated functioning of multiple physiological systems. Renal failure can affect the functioning of several of these systems which results in low levels of peak oxygen uptake. This review examines the determinants of oxygen uptake as defined by the Fick Equation, and presents data from studies that have reported these physiological measures. It becomes clear that there are many factors that may limit peak oxygen uptake in these patients and any one mechanism may be difficult to identify.