STUDY DESIGN: Systematic literature review. OBJECTIVES: To investigate whether quadriceps atrophy is present in the affected limb of individuals with patellofemoral pain (PFP). BACKGROUND: PFP is a common condition. Atrophy of the quadriceps femoris, in particular the vastus medialis obliquus, is often assumed to be present by clinicians, and its resolution may underpin the reported effectiveness of quadriceps strengthening intervention in PFP rehabilitation. METHODS: A systematic search of the literature was conducted to identify studies that measured the size of the quadriceps in individuals with PFP. Meta-analyses were performed to determine whether quadriceps size in limbs with PFP differed from that in comparison limbs. Separate meta-analyses were performed for quadriceps size measured as girth and quadriceps size measured with imaging (thickness, cross-sectional area, and volume). RESULTS: Ten studies were included in this review. The meta-analysis of girth measurements (3 studies) found no atrophy in limbs with PFP (P = .638). The meta-analyses for imaging techniques (thickness, cross-sectional area, or volume measurements) showed atrophy in the limb with PFP compared to both the asymptomatic limb (3 studies) (P = .036) and limbs from a comparison group (3 studies) (P = .001). The single study that compared the vastus medialis obliquus and vastus lateralis in individuals with PFP found atrophy of both the vastus medialis obliquus and vastus lateralis but no significant difference in the amount of atrophy between them (P = .179). CONCLUSION: Quadriceps muscle atrophy was shown to be present in PFP when analyzed by imaging, but not by girth measures. Insufficient data were available to determine if there was greater atrophy of the vastus medialis obliquus than the vastus lateralis. These findings support the rationale for use of quadriceps strengthening as part of a rehabilitation program for PFP.