The Musculoskeletal Function Assessment (MFA) instrument, a health status instrument with 100 self-reported health items, was designed for use with the broad range of patients with musculoskeletal disorders of the extremities commonly seen in clinical practice. In this paper, we report on its criterion and construct validity. Criterion validity was tested against physicians' ratings of patient functioning (e.g., upper functioning, lower functioning, daily activities, recreational functioning, emotional adjustment, and overall functioning) and standard clinical measures (e.g., grip strength, walking speed, fine motor skills, knee and elbow strength, and range of motion). Significant correlations (p ≤ 0.05) between its scores, physicians' ratings, and clinical measures support the MFA's criterion validity. Construct validity was demonstrated against existing measures of health status (e.g., measures of lower and upper mobility, activity level and satisfaction, health status, social support, pain, emotional status, and quality of life), in accordance with clinical hypotheses about the effect of musculoskeletal disorders on functioning (e.g., type and number of problems, severity of illness or injury, and comorbidities) and by an analysis of demographic characteristics (e.g., sex, education, income, health insurance, and employment) against the MFA scores. Discriminant construct validity was supported in an analysis of MFA scores by patient disease groups (p ≤ 0.01).