This paper presents a conceptual model for the pathogenesis of work-related musculoskeletal disorders. The model contains sets of cascading exposure, dose, capacity, and response variables, such that response at one level can act as dose at the next. Response to one or more doses can diminish or increase the capacity for responding to successive doses. The model is used as a framework for discussing the development of work-related muscle, tendon, and nerve disorders. It is intended as a beginning, to be modified to explain new findings as they become available. In research, it can help to identify areas needing additional data for the development and expression of work-related musculoskeletal disorders. Researchers can use it to design laboratory and field studies. In practice, it demonstrates the relationship between common exposure factors and different responses. This information can be used to evaluate and design jobs for the prevention of work-related musculoskeletal disorders.