A functional approach based on the model of the functional system incorporates all aspects relevant to disorders of the loco-motor system. Most disturbances the system can compensate. If compensating mechanisms are not sufficient, the system decompensates, and symptoms develop. It is important to search not only for structural changes but also for somatic dysfunction, psychosocial factors, and changes in neuromodulation. On this basis, treatment strategies can be developed. If there are complex disturbances on different levels, a multimodal interdisciplinary treatment is indicated. The model of the functional system highlights the important role of manual medicine in the diagnostics, treatment, prevention, and rehabilitation of disorders of the loco-motor system.