Anterior cruciate ligament (ACL) injuries are highly prevalent during sporting activities. These injuries often are associated with maneuvers involving landing or sudden change in direction, which are thought to "destabilize" the knee joint and cause ACL rupture. ACL injuries can affect one's mobility and quality of life because of abnormal locomotion and consequent knee pain. This review presents key findings from prior biomechanics studies that aimed to understand ACL injury mechanisms. These studies, ranging from motion analyses and in vitro impact tests to knee finite element simulations and multibody dynamics musculoskeletal simulations, have collectively revealed the multifactorial nature of ACL injury mechanisms. Therefore, the second part of this review addresses the strong need to develop prophylactic strategies that can attenuate the factors involved in ACL injury mechanisms, such that the knee joint can be protected from ACL injuries. Previous studies have emphasized strategies such as knee bracing and strength training of important muscle groups. Although these strategies were intended to mitigate ACL injury-causing factors, their clinical outcomes remain controversial. Given the rapid progress of technologies in this area, however, the current state of uncertainty will gradually lead to prospective biomechanics research that can adopt a multifactorial approach toward protecting the ACL from injury.