Changes of direction (CODs) are key manoeuvres linked to decisive moments in sport and are also key actions associated with lower limb injuries. During sport athletes perform a diverse range of CODs, from various approach velocities and angles, thus the ability to change direction safely and quickly is of great interest. To our knowledge, a comprehensive review examining the influence of angle and velocity on change of direction (COD) biomechanics does not exist. Findings of previous research indicate the biomechanical demands of CODs are 'angle' and 'velocity' dependent and are both critical factors that affect the technical execution of directional changes, deceleration and reacceleration requirements, knee joint loading, and lower limb muscle activity. Thus, these two factors regulate the progression and regression in COD intensity. Specifically, faster and sharper CODs elevate the relative risk of injury due to the greater associative knee joint loading; however, faster and sharper directional changes are key manoeuvres for successful performance in multidirectional sport, which subsequently creates a 'performance-injury conflict' for practitioners and athletes. This conflict, however, may be mediated by an athlete's physical capacity (i.e. ability to rapidly produce force and neuromuscular control). Furthermore, an 'angle-velocity trade-off' exists during CODs, whereby faster approaches compromise the execution of the intended COD; this is influenced by an athlete's physical capacity. Therefore, practitioners and researchers should acknowledge and understand the implications of angle and velocity on COD biomechanics when: (1) interpreting biomechanical research; (2) coaching COD technique; (3) designing and prescribing COD training and injury reduction programs; (4) conditioning athletes to tolerate the physical demands of directional changes; (5) screening COD technique; and (6) progressing and regressing COD intensity, specifically when working with novice or previously injured athletes rehabilitating from an injury.