Several factors can predispose individuals to a greater risk of anterior cruciate ligament (ACL) injury. An ACL injury occurs during activities such as cutting, landing, and contact sports. At the same time, given the exposure to risk activities, females run a 1.7-fold greater risk to sustain an ACL injury compared with males. The ACL injury risk is highest for individuals between 14 and 25 years of age. Neuromuscular deficits, such as a reduced ability to control trunk, hip, and knee abduction movements during landing and cutting movements, as well as deficits in strength relative to body weight in the hip muscles or the hamstrings relative to the quadriceps, may expose the ACL to greater forces and increase the associated risk of injury. Neuromuscular deficits related to ACL injury risk are more common in females compared with males. Moreover, genetic and anatomic characteristics, such as increased femoral notch width, increased condylar depth, increased posterior tibial slope, cartilage and meniscal injuries, generalized joint hypermobility, and previous ACL injuries in the immediate family, may predispose an individual to injury. Our knowledge of whether psychological and psychosocial factors may predispose individuals to ACL injury is scarce, but preliminary evidence indicates that individuals exposed to high levels of perceived stress and fatigue might run an increased risk. In addition, low competence-based self-esteem and sleeping an average of less than 8 hours a night, together with quick changes in training volume, may increase the sports injury risk.