Study Design Randomized clinical trial. Objectives To determine if females with patellofemoral pain syndrome (PFPS) who perform hip strengthening prior to functional exercises demonstrate greater improvements than females who perform quadriceps strengthening prior to the same functional exercises. Background Although PFPS has previously been attributed to quadriceps dysfunction, more recent research has linked this condition to impairment of the hip musculature. Lower extremity strengthening has been deemed an effective intervention. However, research has often examined weight-bearing exercises, making it unclear if increased strength in the hip, quadriceps, or both is beneficial. Methods Thirty-three females with PFPS performed either initial hip strengthening (hip group) or initial quadriceps strengthening (quad group) for 4 weeks, prior to 4 weeks of a similar program of functional weight-bearing exercises. Self-reported pain, function, and functional strength were measured. Isometric strength was assessed for hip abductors, external rotators, and knee extensors. A mixed-model analysis of variance was used to determine group differences over time. Results After 4 weeks, there was less mean ± SD pain in the hip group (2.4 ± 2.0) than in the quad group (4.1 ± 2.5) (P = .035). From baseline to 8 weeks, the hip group demonstrated a 21% increase (P<.001) in hip abductor strength, while that remained unchanged in the quad group. All participants demonstrated improved subjective function (P<.006), objective function (P<.001), and hip external rotator strength (P = .004) from baseline to testing at 8 weeks. Conclusion Both rehabilitation approaches improved function and reduced pain. For patients with PFPS, initial hip strengthening may allow an earlier dissipation of pain than exercises focused on the quadriceps. Level of Evidence Therapy, level 2b-. J Orthop Sports Phys Ther 2011;41(8):560–570. Epub 7 June 2011. doi:10.2519/jospt.2011.3499