Regenerative medicine represents “an interdisciplinary field that applies the principles of engineering and life sciences towards the development of biological substitutes that restore, maintain or improve tissue function.” The protagonists of this therapeutic strategy are cells (adult, mesenchymal, etc.), natural and/or synthetic biomaterials, and growth factors. In orthopedic field, the study of this innovative technology has involved surgeons and researchers for a long time to implement its use for repair and /or replace damaged musculoskeletal tissues. Growth factors are proteins capable of stimulating cell proliferation and differentiation and preventing apoptosis. They are typical “signal” molecules used for communication between the cells of an organism; for example, cytokines (inflammatory molecules) or hormones that bind to specific receptors on the cell membrane of their targets. This chapter provides an overview of the growth factors active in musculoskeletal tissue regeneration highlighting their activities with a particular emphasis on those being pursued for clinical translation.