Muscle pain after unaccustomed exercise is believed to result from repetitive active lengthening of skeletal muscle. This "eccentric exercise" initiates a sequence of events that includes muscle cytoskeletal breakdown, inflammation, and remodeling such that subsequent exercise sessions result in less injury and soreness. Recent studies of eccentric exercise using well-defined animal models have identified the mechanical and cellular events associated with the injury-repair process. In addition, neurophysiologic studies have elucidated mechanisms of pain that operate in skeletal muscle. Taken together, these studies improve our understanding of the muscle injury process and will lead to rational therapeutic interventions to facilitate recovery.