PURPOSE/OBJECTIVES: To estimate and compare responsiveness of standardized self-reported measures of musculoskeletal symptoms (MSSs) and physical functioning (PF) during treatment with aromatase inhibitors (AIs). DESIGN: Prospective, longitudinal study. SETTING: Park Nicollet Institute and North Memorial Cancer Center, both in Minneapolis, MN. SAMPLE: 122 postmenopausal women with hormone receptor-positive breast cancer. METHODS: MSSs and PF were assessed before starting AIs and at one, three, and six months using six self-reported MSSs measures and two PF tests. MAIN RESEARCH VARIABLES: MSSs and PF changes from baseline to six months. FINDINGS: Using the Breast Cancer Prevention Trial-Musculoskeletal Symptom (BCPT-MS) subscale, 54% of participants reported MSSs by six months. Scores from the BCPT-MS subscale and the physical function subscales of the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) were most responsive to changes over six months. CONCLUSIONS: BCPT-MS, AUSCAN, and WOMAC were the most responsive instruments for measuring AI-associated MSSs. IMPLICATIONS FOR NURSING: Assessment and management of MSSs are important aspects of oncology care because MSSs can affect functional ability and AI adherence. KNOWLEDGE TRANSLATION: The three measures with the greatest sensitivity were the BCPT-MS, AUSCAN, and WOMAC questionnaires. These measures will be useful when conducting research on change in MSSs associated with AI treatment in women with breast cancer.