The patellofemoral joint is crucial to the mechanical function of the knee extension mechanism. The patella intricately articulates with the trochlear groove of the femur and allows the transfer of quadriceps force to the tibia. It is difficult to measure patellar motion because it moves beneath skin and soft tissues;​ therefore, when studying the knee extensor mechanism, patellar kinematics are often simplified to functions of knee flexion angle. Since the patellofemoral joint moves with six-degrees-of-freedom, this oversimplification does not provide a full understanding of the patella’s mechanical contributions. Furthermore, these simplifications do not include subject-specific shape effects that influence the mechanical function of the joint. In this work, I used statistical shape modeling and data-driven musculoskeletal models to investigate the impact of patellofemoral morphology on knee mechanics. I found that patella shape modulates the ratio of quadriceps force and patellar ligament force across individuals. I then identified functional differences caused by energetically different dynamic motions in walking and running. I simulated knee motion with a lower-limb musculoskeletal model to investigate the knee extension moment arm and the importance of its variation with patella articulation. I found that out-of-plane motion and knee flexion angle affects the moment arm length throughout knee motion. This variation may have mechanical importance in knee angular acceleration with a constant applied force. Finally, I examined patellofemoral mechanics in individuals with patellofemoral pain with and without foot orthoses as an intervention. Since patellofemoral pain is thought to be induced by irregular lower-limb mechanics, medial wedge foot orthoses are designed to alter ankle mechanics and increase the knee adduction moment to reduce pain. I generated a statistical shape model to relate knee morphologies to orthotic response. Modes of variation describe shape features that increased knee adduction moment with foot orthoses. Contrary to clinical rationale, foot orthoses increased patellar contact pressure during midstance though the response is likely subject-specific. This work emphasizes the importance of using subject-specific parameters and three-dimensional motion when researching patellofemoral mechanics. A better understanding of the patella’s functional role and the shape-function relationship will ultimately improve clinical recommendations and development of interventions to promote ideal patellofemoral motion.