One of the consequences of sustaining exercise for 90 minutes of football match-play is that the capability of muscle to generate force declines. This impairment is reflected in the decline of work-rate towards the late part of the game. Causes of this phenomenon, which is known as fatigue, and some of its consequences are considered in this article. The stores of muscle glycogen may be considerably reduced by the end of the game, especially if there has not been a tapering of the training load. Thermoregulatory strain may also be encountered, resulting in a fall in physical performance, or there may be a reduced central drive from the nervous system. The decline in muscle strength may increase the predisposition to injury in the lower limbs. Central fatigue may also occur with implications for muscle performance. Strategies to offset fatigue include astute use of substitutions, appropriate nutritional preparation and balancing pre-cooling and warm-up procedures. There is also a role for endurance training and for a pacing strategy that optimizes the expenditure of energy during match-play.