The literature suggests that a Grade II medial collateral ligament (MCL) injury in combination with anterior cruciate ligament (ACL) injury will heal naturally and not compromise patient outcome following ACL reconstruction. Evidence based on bone-patella tendon-bone autograft use is stronger than evidence supporting anatomically placed soft tissue graft use. Current ACL reconstruction practices make greater use of soft tissue grafts, differing fixation methods, and anatomically lower placement on the inner wall of the lateral femoral condyle. Anatomical graft placement aligns the femoral bone tunnel more directly with valgus knee loading forces. Differences in the soft tissue graft-bone tunnel integration and ligamentization timetable following ACL reconstruction also increase concerns regarding residual Grade II MCL laxity and functional deficiency during accelerated functional rehabilitation. MCL dysfunction may increase susceptibility to early ACL graft slippage, elongation, outright failure, and medial femoral condyle lift-off with valgus knee loading. This concept paper discusses the potential role of growth factors and bio-scaffolds for improving Grade II MCL injury healing and mechanical integrity when the injury occurs in combination with an ACL injury that is reconstructed with a soft tissue graft and an anatomical surgical approach.