High incidences of non-contact anterior cruciate ligament (ACL) injury, frequent requirements for ACL reconstruction, and limited understanding of ACL mechanics have engendered considerable interest in quantifying the ACL loading mechanisms. Although some progress has been made to better understand non-contact ACL injuries, information on how and why non-contact ACL injuries occur is still largely unavailable. In other words, research is yet to yield consensus on injury mechanisms and risk factors. Biomechanics, video analysis, and related study approaches have elucidated to some extent how ACL injuries occur. However, these approaches are limited because they provide estimates, rather than precise measurements of knee - and more specifically ACL - kinematics at the time of injury. These study approaches are also limited in their inability to simultaneously capture many of the contributing factors to injury.This paper aims at elucidating and summarizing the key challenges that confound our understanding in predicting the mechanisms and subsequently identifying risk factors of non-contact ACL injury. This work also appraise the methodological rigor of existing study approaches, review testing protocols employed in published studies, as well as presents a possible coupled approach to better understand injury mechanisms and risk factors of non-contact ACL injury. Three comprehensive electronic databases and hand search of journal papers, covering numerous full text published English articles were utilized to find studies on the association between ACL and injury mechanisms, ACL and risk factors, as well as, ACL and investigative approaches. This review unveils that new research modalities and/or coupled research methods are required to better understand how and why the ACL gets injured. Only by achieving a better understanding of ACL loading mechanisms and the associated contributing factors, one will be able to develop robust prevention strategies and exercise regimens to mitigate non-contact ACL injuries.