Musculoskeletal disorders are a spectrum of diseases and disorders that affect bones, joints, muscles, and related supportive tissues, often referred to as the musculoskeletal system. In this context, they include osteoarthritis, osteoporosis, autoimmune rheumatic diseases, musculoskeletal injuries caused by acute or chronic trauma as well as those resulting from congenital disorders and infections. Collectively, these diseases are a major cause of debilitating, chronic pain, physical disability and reduced quality of life for a huge number of individuals across the globe. Musculoskeletal diseases are the leading cause of global disability, according to the World Health Organization, with osteoarthritis alone affecting about 303 million people worldwide. The costs associated with musculoskeletal conditions in terms of direct expenditure for surgeries and medicines, and indirect costs such as loss of productivity and work incapacity, are massive. As described above, conventional therapies for these diseases mainly target symptom relief and functional restoration but do not restore the anatomical integrity of the tissue affected or stop disease progression and can include drugs that provide analgesic or anti-inflammatory effects plus surgical interventions (e.g. knee joint replacement) that carry high surgical risk and general complications. Thus, in this scenario, regenerative therapies constitute a new promising dimension for the improvement of the care of patients affected by MSci diseases. Indeed, the area of regenerative medicine—including cell-therapies, tissue engineering and bioprinting approaches—represents a prompt breakthrough for the treatment and even for the reversal of tissue and organ damage. The goal of this chapter will be to describe novel regenerative therapies and their recent applications, reporting on the latest developments in the field and providing details about their feasibility in clinical settings. Moreover, we will illustrate how these innovative approaches have the potential to change the concept of treatment of these complex and multifaceted diseases. Hopefully, this will contribute to clarify the potential of these regenerative therapies, which, once made available, will become the new standard treatment of these diseases in the near future.