Exercise-induced skeletal muscle damage results in a remarkable number of localized and systemic changes, including release of intracellular proteins, delayed onset muscle soreness, the acute-phase response, and an increase in skeletal muscle protein turnover. These exercise-induced adaptations appear to be integral to the repair of the damaged muscle and may be essential for hypertrophy. Chronic exercise produces adaptations in skeletal muscle, resulting in increased capacity of oxidative metabolism; the repair of damaged muscle resulting in hypertrophy may be an important mechanism for protection against further exercise-induced damage. Although the release of CK from skeletal muscle following damage is a commonly observed phenomenon, circulating CK activity is not a quantitative and, in some cases, even a qualitative indicator of skeletal muscle damage. Eccentric exercise-induced skeletal muscle damage offers an opportunity to investigate the signals and modulators of the repair of muscle damage, a process that may be central to the adaptations in muscle as a result of chronic activity.