Despite extensive research, we still do not fully understand the biological mechanisms that underlie a female's increased susceptibility for suffering a noncontact ACL injury. While sex differences in neuromuscular control are often implicated, prevention efforts addressing these differences have not resulted in a profound or sustainable reduction in injury rates. This paper will explore two likely scenarios that explain this greater susceptibility in females: (1) females have a structurally weaker ligament that is more prone or susceptible to failure at a given load (scenario #1), or (2) females develop less knee protection and experiences higher relative loads on the ACL (scenario #2). While we have learned much over the last two decades about ACL injury risk in females, much remains unknown. Continued research is of paramount importance if we are to effectively identify those females who are at greatest risk for injury and effectively reduce their susceptibility through appropriate interventions.