In this article, the authors assess the natural history of osteoarthritis in the anterior cruciate ligament deficient knee, and examine the factors which may influence its progression: meniscal resection, osteochondral lesions, malalignment, concomitant ligamentous pathology, biological factors, and surgery. The role of anterior cruciate reconstruction, high tibial osteotomy in the coronal and sagittal plane, meniscal allografts, and combined procedures will be reviewed. Finally, the authors' approach to this increasingly common problem is presented.