Study Design Prospective cohort. Objective To investigate fear-avoidance eliefs across different anatomical regions for patients with musculoskeletal pain. Background Fear-avoidance beliefs were first widely studied in patients with low back pain. The early results of studies involving patients with cervical spine, knee, and shoulder disorders suggest that fear-avoidance beliefs have the potential to influence pain and function in different anatomical regions. However, very few prospective studies of fear-avoidance beliefs involve multiple anatomical regions. Methods The sample of this study consisted of 313 patients (mean age, 45.5 years; 115 males, 198 females) seeking outpatient physical therapy for cervical spine (n = 63), upper extremity (n = 58), lumbar spine (n = 79), or lower extremity (n = 113) complaints. During the intake session, patients completed the Fear-Avoidance Beliefs Questionnaire physical activity scale (FABQ-PA), modified for the appropriate anatomical location. Patients also rated pain intensity and function on the Therapeutic Associates Outcomes System (TAOS) Functional Index at intake and discharge. The collection of treatment-related parameters included the number of visits, calendar days of physical therapy, and treatment received. FABQ-PA scores were compared across anatomical regions. Elevated FABQ-PA scores and anatomical regions were also investigated for association with intake pain and function, clinical outcomes, and treatment utility parameters. Results Similar FABQ-PA levels were observed across the 4 anatomical regions (P>.05). Number of visits, calendar days of physical therapy, and treatment received did not differ between elevated and lower fear-avoidance belief levels (P>.05). Findings for pain intensity and function were similar for each anatomical region. Patients with elevated fear-avoidance beliefs had higher intake scores (P<.05), larger improvements (P<.05), but similar discharge scores (P>.05), compared to those with lower fear-avoidance beliefs. Conclusions These data suggest that, in patients with cervical, upper extremity, lumbar, or lower extremity complaints, fear-avoidance beliefs may have a similar influence on intake and change scores for pain intensity and function. General assessment of fear-avoidance beliefs using the FABQ-PA, especially to predict change scores, may be appropriate for use in patients with various musculoskeletal pain conditions. J Orthop Sports Phys Ther 2011;41(4):249–259, Epub 18 February 2011. doi:10.2519/jospt.2011.3488