Contralateral anterior cruciate ligament (ACL) injuries are together with the risk of developing osteoarthritis of the knee and the risk of re-rupture/graft failure important aspects to consider after an ACL injury. The aim of this review was to perform a critical analysis of the literature on the risk factors associated with a contralateral ACL injury. A better understanding of these risk factors will help in the treatment of patients with unilateral ACL injuries and in the development of interventions designed to prevent contralateral ACL injuries. A Medline search was conducted to find studies investigating risk factors for a contralateral ACL injury, as well as studies where a contralateral ACL injury was the outcome of the study. Twenty studies describing the risk of a contralateral ACL rupture, or specific risk factors for a contralateral ACL injury, were found and systematically reviewed. In 13 of these studies, patients were followed prospectively after a unilateral ACL injury. The evidence presented in the literature shows that the risk of sustaining a contralateral ACL injury is greater than the risk of sustaining a first time ACL injury. Return to a high activity level after a unilateral ACL injury was the most important risk factor of sustaining a contralateral ACL injury. There was inconclusive evidence of the relevance of factors such as female gender, family history of ACL injuries, and a narrow intercondylar notch, as risk factors for a contralateral ACL injury. Risk factors acquired secondary to the ACL injury, such as altered biomechanics and altered neuromuscular function, affecting both the injured and the contralateral leg, most likely, further increase the risk of a contralateral ACL injury. This literature review indicates that the increased risk of sustaining a contralateral ACL injury should be contemplated, when considering the return to a high level of activity after an ACL injury.