An adequately functioning musculoskeletal system is a key factor for functional capacity, independence, and good quality of life. Impaired functional capacity and degenerative diseases of the musculoskeletal organs are one of the most prevalent and increasing sources of morbidity and suffering. Physical activity positively influences most structural components of the musculoskeletal system that are related to functional capabilities and the risk of degenerative diseases. Physical activity also has the potential to postpone or prevent prevalent musculoskeletal disorders, such as mechanical low back pain, neck and shoulder pain, and osteoporosis and related fractures. Exercise can contribute to the rehabilitation of musculoskeletal disorders and recovery from orthopedic surgery. A substantial part of the age-related decline in functional capabilities is not due to aging per se but to decreased and insufficient physical activity. Physical activity has great potential to favorably influence both the normal and pathological structures, functions, and processes. Musculoskeletal benefits of physical activity can be attained by people of all ages and with various diseases. This potential is substantial because many benefits are gained by activity which is moderate in amount and intensity. Scientific evidence is sufficient to recommend regular lifelong physical activity as part of a healthy lifestyle for everyone in order to enhance musculoskeletal health and functions for individual and population levels. However, several important issues regarding the effects, effectiveness, feasibility, and safety of exercise to improve various aspects of musculoskeletal health and functional capabilities need further research.