This systematic review explored associations between smoking and health outcomes involving the musculoskeletal system. AMSTAR criteria were followed. A comprehensive search of PubMed, Web of Science, and Science Direct returned 243 articles meeting inclusion criteria. A majority of studies found smoking has negative effects on the musculoskeletal system. In research on bones, smoking was associated with lower BMD, increased fracture risk, periodontitis, alveolar bone loss, and dental implant failure. In research on joints, smoking was associated with increased joint disease activity, poor functional outcomes, and poor therapeutic response. There was also evidence of adverse effects on muscles, tendons, cartilage, and ligaments. There were few studies on the musculoskeletal health outcomes of secondhand smoke, smoking cessation, or other modes of smoking, such as waterpipes or electronic cigarettes. This review found evidence that suggests tobacco smoking has negative effects on the health outcomes of the musculoskeletal system. There is a need for further research to understand mechanisms of action for the effects of smoking on the musculoskeletal system and to increase awareness of healthcare providers and community members of the adverse effects of smoking on the musculoskeletal system.