Skeletal muscle is significantly adaptable to stimuli such as physical activity. After conditions of damaging activity, such as eccentric exercise, skeletal muscle tissue undergoes extensive remodelling due to the mechanical stress and subsequent inflammation due to the exercise-induced muscle damage. Repair and remodelling of muscle fibres is directed by a host of factors, such as the activity of satellite cells, the initiation and timing of inflammatory cell infiltration, and the contribution of various cells and structures within the muscle microenvironment. Furthermore, other variables influence the degree of remodelling, such as post-exercise recovery and sex. This book chapter will discuss in detail how these factors influence the exercise-induced muscle damage response.