To estimate and compare responsiveness of standardized self-reported measures of musculoskeletal symptoms (MSSs) and physical functioning (PF) during treatment with aromatase inhibitors (AIs). Prospective, longitudinal study. Park Nicollet Institute and North Memorial Cancer Center, both in Minneapolis, MN. 122 postmenopausal women with hormone receptor-positive breast cancer. 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. MSSs and PF changes from baseline to six months. 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. BCPT-MS, AUSCAN, and WOMAC were the most responsive instruments for measuring AI-associated MSSs. Assessment and management of MSSs are important aspects of oncology care because MSSs can affect functional ability and AI adherence. 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.