Injury prevention frameworks are critical for preventing musculoskeletal injury and improving rehabilitation outcomes. However, their relative successes in translation arguably rely on two interlinked components: (1) the quality of the empirical evidence used to develop the intervention (content), and (2) the effective application of behavior change and motivation principles to optimise participant adherence and engagement (delivery). The purpose of this commentary is to develop an injury prevention and rehabilitation framework using the best available physics-based simulation, biomechanics, and behavior change research. The intervention as a whole is entitled biomechanically-informed training (BIT). While investigators have previously examined the relative merits of different training genres (e.g., plyometric, balance, resistance), what makes BIT novel is that it explicitly targets the biomechanical mechanisms that mitigate musculoskeletal injury risk (i.e., force) in ways that are underpinned by established behavior change principles. The four pillars of BIT refer to focused exercise use, irrespective of the training genre, to improve an individual's: (1) knee flexion dynamics, (2) dynamic trunk control, (3) gastrocnemius muscle strength, and (4) hip muscular strength. We also present experimental data from two independent training studies verifying the efficacy of BIT for the prevention of knee and anterior cruciate ligament (ACL) injury.