The debate about work-relatedness of musculoskeletal disorders (MSDs) reflects both confusion about epidemiologic principles and gaps in the scientific literature. The physical ergonomic features of work frequently cited as risk factors for MSDs include rapid work pace and repetitive motion, forceful exertions, non-neutral body postures, and vibration. However, some still dispute the importance of these factors, especially relative to non-occupational causes. This paper addresses the controversy with reference to a major report recently commissioned by the US Congress from the National Research Council (NRC) and Institute of Medicine (IOM) (2001). The available epidemiologic evidence is substantial, but will benefit from more longitudinal data to better evaluate gaps in knowledge concerning latency of effect, natural history, prognosis, and potential for selection bias in the form of the healthy worker effect. While objective measures may be especially useful in establishing a more secure diagnosis, subjective measures better capture patient impact. Examination techniques still do not exist that can serve as a "gold standard" for many of the symptoms that are commonly reported in workplace studies. Finally, exposure assessment has too often been limited to crude indicators, such as job title. Worker self-report, investigator observation, and direct measurement each add to understanding but the lack of standardized exposure metrics limits ability to compare findings among studies. Despite these challenges, the epidemiologic literature on work-related MSDs-in combination with extensive laboratory evidence of pathomechanisms related to work stressors-is convincing to most. The NRC/IOM report concluded, and other reviewers internationally have concurred, that the etiologic importance of occupational ergonomic stressors for the occurrence of MSDs of the low back and upper extremities has been demonstrated.