Effectively addressing population-level variability within orthopedic analyses requires robust data sets that span the target population and can be greatly facilitated by statistical methods for incorporating such data into functional biomechanical models. Data sets continue to be disseminated that include not just anatomical information but also key mechanical data including tissue or joint stiffness, gait patterns, and other inputs relevant to analysis of joint function across a range of anatomies and physiologies. Statistical modeling can be used to establish correlations between a variety of structural and functional biometrics rooted in these data and to quantify how these correlations change from health to disease and, finally, to joint reconstruction or other clinical intervention. Principal component analysis provides a basis for effectively and efficiently integrating variability in anatomy, tissue properties, joint kinetics, and kinematics into mechanistic models of joint function. With such models, bioengineers are able to study the effects of variability on biomechanical performance, not just on a patient-specific basis but in a way that may be predictive of a larger patient population. The goal of this paper is to demonstrate the broad use of statistical modeling within orthopedics and to discuss ways to continue to leverage these techniques to improve biomechanical understanding of orthopedic systems across populations.