Osteoarthritis is widely believed to result from local mechanical factors acting within the context of systemic susceptibility. Previous studies have demonstrated that malalignment is a potent predictor of disease progression in patients with osteoarthritis of the knee. Malalignment also mediates the effects of other risk factors, including obesity, quadriceps strength, laxity, and stage of disease. Recent studies have had conflicting results regarding whether malalignment increases the risk of incident tibiofemoral osteoarthritis. While the evidence is conflicting, malalignment appears to play a smaller role in incident disease. Certain local factors within the joint, such as tibiofemoral congruence, integrity of the anterior cruciate ligament, and meniscal degeneration and position, appear to play a role in determining alignment. It is also apparent that malalignment changes with disease progression and is itself possibly influenced by structural changes within the joint.