Muscle fatigue can be caused by a number of different mechanisms that result in an acute reduction in the ability to perform a motor task. These mechanisms include the physiological processes that range from the motivation associated with performing the task through to the force exerted by the contractile proteins once they are activated. Two issues are examined in this brief review. First, the role of mechanisms located in the central nervous system (central factors) in the fatigue experienced by human subjects. Second, the importance of task conditions (task dependency) on the fatigue mechanisms involved in a particular performance. The literature documents a prominent role for central factors in the development of muscle fatigue. This role is examined by considering subject motivation, the descending signals sent by suprasegmental centres (central command) and motor unit behaviour. The significance of these or other mechanisms, however, appears to depend on the details of the task. Variation in such requirements as contraction intensity or duration, speed of movement, or type of muscle contraction alters the role of the different mechanisms in limiting performance. Unfortunately, few studies have examined these effects systematically. The field of muscle fatigue would benefit substantially from studies that determined the boundary conditions for the different fatigue mechanisms.