While it is generally accepted that most partial and isolated medial collateral ligament (MCL) injuries can be treated non-operatively, ideal treatment of the MCL in multi-ligament knee injuries remains controversial. High failure rates with repair of the posterolateral corner in the multi-ligament injured knee have been recently reported, favoring reconstruction instead. The same maybe true for MCL injuries, however evidence-based treatment recommendations are lacking in the current orthopedic literature. The purpose of this study was to perform an evidence-based systematic review of the operative management (repair and/or reconstruction) of the MCL in the setting of multi-ligament knee injuries. A comprehensive search of MEDLINE and the Cochrane databases for all relevant articles published in English from 1978 to 2008 on the outcomes of surgical management (repair and/or reconstruction) of the MCL in the setting of combined ligament injuries was performed. Inclusion criteria included articles published in (1) English, (2) on human subjects, (3) between the years of 1978 and 2008, (4) had minimum 12-month follow-up, with a mean of at least 24 months, (5) on surgical management of MCL injuries, (6) associated with multi-ligament injuries (three or more ligaments) and/or knee dislocation, and (7) reported objective outcome data on the respective patient cohorts. Exclusion criteria consisted of technique papers, case reports, studies that included fractures associated with MCL injury and those that included pediatric patients. The review identified eight relevant studies. Five articles focused on MCL repair, while three articles focused on MCL reconstruction. No prospective studies compared MCL repair or reconstruction with non-operative treatment or directly compared MCL reconstruction with MCL repair. Currently there is a paucity of objective data on the outcomes regarding surgical management of MCL tears in the combined ligament injured knee. This systematic review demonstrated satisfactory results in both repair and reconstruction groups. Future objective outcome-based studies as well as comparative studies are needed to further evaluate the optimal treatment modality before evidence-based recommendations can be made. Therefore, individual treatment decisions for each patient should be based on the characteristics and nature of the injury.