The muscles of the lower limb play an important role in the genesis and management of knee osteoarthritis (OA). This article outlines the influence of muscle activity on knee joint loading, the deficits in muscle function observed in people who have knee OA, and available evidence pertaining to the role of muscle in the development and progression of knee OA. It also discusses whether muscle deficits can be modified in knee OA and whether improvements in muscle function lead to improved symptoms and joint structure. It concludes with a discussion of exercise prescription for muscle rehabilitation in knee OA.