Fixed rotation of either the femur or tibia has a significant influence on the patellofemoral joint contact areas and pressures. This is due to the anatomic asymmetry in the knee with respect to all planes, as well as the laterally directed force vector that naturally exists in bipedal lower-limb biomechanics. Specifically, femoral rotation results in an increase in patellofemoral contact pressures on the contralateral facets of the patella, and tibial rotation results in an increase in patellofemoral contact pressures on the ipsilateral facets of the patella. This difference can be elucidated when one considers that rotation of the femur is biomechanically different than rotation of the tibia. For both tibial and femoral rotations, the patella's distal attachment to the tibial tubercle influences the direction of patellar movement. The biomechanical evidence reviewed in this manuscript suggests that the determining factor in patellofemoral pathology is the derangement of normal joint mechanics. However, despite considerable experimental data supporting this position, there also are theories that suggest otherwise. This illustrates a very important point in patellofemoral joint pathology, where no one factor may be the sole defining etiology. Instead, the patellofemoral joint is one of the most complex diarthrodial joints in the body and there are a number of etiologic factors that can lead to pathology. This should be considered for developing repair and rehabilitation strategies.