Manual Therapy is one of the most widely used therapeutic solutions in the treatment of pain and musculoskeletal disorders. Its evolution began several centuries ago and culminated in the modern reference methods in the field of physiotherapy, osteopathy, and chiropractic, which mainly address the treatment of joint and myofascial tissues. The advent of evidence-based medicine and the ever-growing literature available in the field of Manual Therapy has led this therapeutic approach to be heavily criticized on the basis of studies that have shown its limitations with regard to manual and palpatory assessment techniques, the poor biomechanical validity of therapeutic methods, and the poor long-term results in the treatment of patients with musculoskeletal pain. A better understanding of the mechanisms underlying the effectiveness of Manual Therapy, as well as of the mediators of the medium-and long-term effectiveness of musculoskeletal rehabilitation processes, has made it possible to reconsider the role of Manual Therapy and the healthcare professionals specializing in manipulative therapy within the framework of the biopsychosocial model, which focuses on the patient and their functionality.