The regeneration of the musculoskeletal system has been widely investigated. There is now detailed knowledge about the organs composing this system. Research has also investigated the zones between individual tissues where physical, mechanical and biochemical properties transition. However, the understanding of the regeneration of musculoskeletal interfaces is still lacking behind. Numerous disorders and injuries can degrade or damage tissue interfaces. Their inability to regenerate can delay the repair and regeneration process of tissues, leading to graft instability, high morbidity and pain. Moreover, the knowledge of the mechanism of tissue interface development is not complete. This review presents an overview of the most recent approaches of the regeneration of musculoskeletal interfaces, describing the latest in vitro, preclinical and clinical studies.