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This review evaluates recently published literature examining various muscle tissue cells and their modulators that determine whether injured skeletal muscle will fully regenerate or become fibrotic.Muscle regeneration is a complex process involving several interacting cell types. Macrophages initiate a cytokine response to injury that both directs the subsequent inflammatory response and promotes nonmyeloid proliferation. Muscle cells and their progenitors produce autocrine and paracrine growth factors that help inhibit or stimulate muscle growth and regeneration. Cells of the connective tissue, including fibroblasts and newly described fibro/adipogenic progenitors, can support myogenic cells and remodel the extracellular matrix. However in certain environments, fibrosis can become a self-perpetuating process leading to incomplete muscle regeneration.Several cell types are involved in the muscle repair process, interacting through multiple signaling molecules and pathways. This provides a richness of potential therapeutic targets to reduce fibrosis and facilitate skeletal muscle regeneration.