Work-related musculoskeletal disorders (MSDs) have accounted for a significant proportion of work injuries and workers' compensation claims in industrialized nations since the late 1980s. Despite epidemiological evidence for the role of repetition and force in the onset and progression of work-related MSDs, complete understanding of these important occupational health problems requires further elucidation of the underlying pathogenesis. Results from several clinical and experimental studies indicate that pathological and/or adaptive tissue changes occur as a consequence of performing repetitive and/or forceful tasks. Here, we review evidence of these tissue changes as revealed by the testing of serum biomarkers. Biomarkers of inflammation (inflammatory cytokines and C-reactive protein), cell stress or injury (malondialdehyde and creatine kinase), and collagen synthesis and degradation (collagen I carboxy-terminal propeptide and type-I collagen cross-linked C-telopeptide, respectively) and their association with MSDs will be reviewed.