Skeletal muscle is a structurally and functionally remarkable tissue composed of multinucleated post-mitotic muscle fibres. These fibres are filled with an exquisite, near crystalline array of assembled contractile proteins, capable of coupling ATP utilization to mechanical muscle contraction. Fully differentiated muscle has an incredible ability to protect and repair itself from significant muscle injuries. In fact, through activation of a resident population of stem cells known as satellite cells, muscle fibres can be completely regenerated, and normal function can be restored in a matter of a few weeks after a major myocellular necrotic injury. The loss of key mechanisms to protect muscle from injuries or loss of the capacity to repair muscle after injury is thought to underlie several forms of muscular dystrophy and also the age-related decline of muscle function. In this Subject Collection, The FEBS Journal highlights articles that review or investigate key mechanisms of muscle repair and regeneration in response to injuries, and the contributions of these pathways to health and disease of skeletal muscle.