As this work is published, at the beginning of the twenty first century, a new perspective of the classic orthopedic enigma of the patellofemoral pain problem is becoming increasingly accepted. It is clear that the decades-old paradigm of a pure structural and biomechanical explanation for the genesis of patellofemoral pain is inadequate, and that a new era has begun with biological factors now being given more consideration. A variable mosaic of pathophysiologic events (often due to simple overload) such as patellofemoral synovitis, retinacular neuromas, patellar tendonitis, and painful increased osseous remodeling of the patellofemoral joint – processes when taken together can be characterized by the term “loss of tissue homeostasis” – can be seen as providing new and alternative explanations for the conundrum of anterior knee pain. It clinically matters little what structural factors may be present in a given joint (such as chondromalacia, patellar tilt, or a Q angle above a certain value) if the pain-free condition of tissue homeostasis is achieved and maintained. Despite recent conceptual advances – represented by this newer biological perspective – much remains to be discovered regarding the patellofemoral joint before it can be said to be fully understood.