Many patient characteristics can affect joint function;​ yet the implications of this for musculoskeletal disorders and their treatment are not well understood. A better understanding of these relationships could aid in clinical decision making and make it easier to better tailor treatments to each patient. In this work, methods to enable the study of patient variability were proposed and used to investigate the relationship among patient characteristics, function, and surgical outcomes. A method to remove bias from waveform data using principal component analysis was introduced that could be used to combine motion analysis data from different laboratories, thus enabling multicentre studies and larger sample sizes. In a second study, patient characteristics and biomechanical measures associated with the ability of valgus unloader braces to reduce predicted medial compartment contact forces were identified. The hip adduction moment during unbraced walking was the best predictor of mechanical brace effectiveness. The remainder of this thesis focused on articular geometry, a source of patient variability that has previously been shown to be correlated with joint function and pathology. Here, a framework was proposed that can be used to predict the causal effects of geometry on function. Knee joint geometry was characterized and manipulated through statistical shape modelling and functional effects on knee kinematics, cartilage contact, and ligament forces were predicted using musculoskeletal simulation. This framework was used to examine the impact of knee joint geometry on functional outcomes of simulated tibial tubercle osteotomy, a surgery that realigns the patellar tendon to treat patellar instability. It was found that knees with shallow patellofemoral geometry were much more sensitive to medial/lateral placement of the patellar tendon insertion than those with deep geometry. Finally, the potential to use these techniques to inform clinical decision making through patient-specific modelling was explored in a case study of a tibial tubercle osteotomy patient.