The current study was performed to characterize how improving vastus medialis obliquus (VMO) function influences the pressure applied to patellofemoral cartilage. An additional focus was characterizing how lateral and medial cartilage lesions influence cartilage pressures. Ten knees were flexed to 408, 608, and 808 in vitro, and forces were applied to represent the VMO and other muscles of the quadriceps group while a thin film sensor measured joint pressures. The knees were loaded with a normal VMO force, with the VMO force decreased by approximately 50%, and with the VMO unloaded. After tests were performed with the cartilage intact, all tests were repeated with a 12-mm-diameter lesion created within the lateral cartilage, with the lateral lesion repaired with silicone, and with a medial lesion created. Based on a two-way repeated measures ANOVA and post-hoc tests, increasing the force applied by the VMO significantly ( p < 0.05) decreased the maximum lateral pressure and significantly increased the maximum medial pressure at each flexion angle. A lateral cartilage lesion significantly increased the maximum lateral pressure, while a medial lesion did not significantly influence the maximum medial pressure. Improving VMO function can reduce the pressure applied to lateral cartilage when lateral lesions are present. Patellofemoral disorders are commonly attributed to an excessive lateral force applied to the patella. Due to the normal valgus orientation of the knee, the quadriceps muscles and the patella tendon act to shift and tilt the patella laterally. Passive resistance provided by the medial retinacular structures and forces due to contact with the trochlear groove resist the forces applied by the quadriceps and the patella tendon. 1,2 An excessive lateral force or inadequate resistance can lead to overloading of the lateral cartilage or lateral instability. 3 Overloading lateral cartilage can lead to areas of cartilage degradation, or lesions. 3,4 Instability episodes damage the medial retinacular restraints and can lead to lesions within the medial cartilage due to the medial facet of the patella contacting the bone on the lateral condyle of the femur. 5,6 Cartilage lesions increase the pressure applied to the surrounding cartilage 7 and can lead to pain due to overloading of the subchondral bone. 3,5,8 Physical therapy regimens prescribed for patellofemoral disorders commonly focus on improving the function of the vastus medialis obliquus (VMO). The force applied by the VMO has a medial component that can help resist the lateral force applied by the other quadriceps muscles. Some studies have indicated that patients with patellofemoral pain generate less force through the VMO than asymptomatic subjects. 9,10 The onset of VMO activity can also be delayed in patients with patellofemoral pain. [11][12][13][14][15] Although studies have indicated that training the VMO improves the strength 16 and activation timing 15 of the VMO, and provides better outcomes than a placebo treatment, 15,17 training ...