This systematic review was designed and conducted in an effort to evaluate the evidence currently available for the many suggested risk factors for work-related musculoskeletal disorders. To identify pertinent literature we searched four electronic databases (Cinahl, Embase, Medline, and The Cochrane Library). The search strategies combined terms for musculoskeletal disorders, work, and risk factors. Only case-control or cohort studies were included. A total of 1,761 non-duplicated articles were identified and screened, and 63 studies were reviewed and integrated in this article. The risk factors identified for the development of work-related musculoskeletal disorders were divided and organized according to the affected body part, type of risk factor (biomechanical, psychosocial, or individual) and level of evidence (strong, reasonable, or insufficient evidence). Risk factors with at least reasonable evidence of a causal relationship for the development of work-related musculoskeletal disorders include: heavy physical work, smoking, high body mass index, high psychosocial work demands, and the presence of co-morbidities. The most commonly reported biomechanical risk factors with at least reasonable evidence for causing WMSD include excessive repetition, awkward postures, and heavy lifting. Additional high methodological quality studies are needed to further understand and provide stronger evidence of the causal relationship between risk factors and work-related musculoskeletal disorders. The information provided in this article may be useful to healthcare providers, researchers, and ergonomists interested on risk identification and design of interventions to reduce the rates of work-related musculoskeletal disorders. 2009 Wiley-Liss, Inc.