AbstractManual medicine is the medical discipline that deals with diagnosis, treatment, and prevention of reversible functional disturbances in the locomotor system and other related organ systems. The current article illustrates neuroanatomical and neurophysiological fundamentals of the mechanisms of manual diagnostics and treatment. Based on the recent literature and consideration of different scientifically based clinical guidelines, the evidence-based effectiveness of manual therapeutic procedures is presented. Acute and chronic low back pain, cervicogenic headache, neck and shoulder pain, radicular arm pain, dysfunctional thoracic pain syndromes, diseases of the rotator cuff, carpal tunnel syndrome, and plantar fasciitis are included. Clinical case studies illustrate the clinical procedures. The term, the origin, and the clinical presence of “osteopathy” are addressed in detail, and the national and international societies of manual medicine (Deutsche Gesellschaft für Manuelle Medizin [DGMM], European Scientific Society of Manual Medicine [ESSOMM], Fédération Internationale de Medicine Manuelle [FIMM]) are portrayed lexically. Finally, contraindications to manual intervention are presented and an outlook on the requirements and possibilities of scientific pain analysis is given in accordance with the preamble of the Deutsche Gesellschaft für Orthopädie und Orthopädische Chirurgie (GSOOC) guidelines on specific low back pain.