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Patients with patellofemoral pain represent a significant challenge to the orthopaedic community. The origin of patellofemoral pain can be directly traced to supraphysiologic mechanical loading and chemical irritation of nerve endings, denoting loss of tissue homeostasis. The persistent biologic cascade of cytokine production can lower the load-acceptance capacity of soft tissues and activate painful osseous remodeling. Activities of daily living can become supraphysiologic loads to sensitized patellofemoral tissues, resulting in chronic reactivation of tissue inflammation. The principles of treatment in most patients with patellofemoral pain consist of protection of sensitive tissues from excessive loading, appropriate antiinflammatory therapy, and nonirritat-ing rehabilitation.