Many therapies have been advocated for treating patellofemoral pain, which suggests little consensus on optimal treatment. We reviewed the high-quality evidence for successful treatment of patellofemoral syndrome based on successful outcome information. To achieve this goal, we undertook a systematic search and critical appraisal of the literature on patellofemoral pain syndrome. Our definition of patellofemoral pain syndrome was broad and included patients with cartilage damage. We found five randomized controlled trials and some follow-up studies. The prognoses for most new cases of patellofemoral pain syndrome are good, although a proportion of patients with this syndrome will have persistent symptoms. Quadriceps muscle exercises were effective in treating this condition, and knee braces were not. Both prostheses and intramuscular glycosaminoglycan polysulfate had encouraging results for patients; however, these results need confirmation. There were many studies of biomechanics, which indicates that there is an assumption that an alteration of abnormal biomechanics would result in clinical benefit. Studies are needed that place more emphasis on the therapeutic benefit. There is limited evidence on which to base therapy, and there needs to be more high-quality research. Studies need to be longer, account for factors that predispose the patients, and have a more standardized means of assessing outcomes.