Osteoarthritis (OA) is the most common form of arthritis and is a major cause of disability in people aged over 65. Despite the major socioeconomic burden imposed by OA, the aetiology of this condition remains unclear. Although controversial, several metabolic factors have been implicated in the disease pathogenesis. Nevertheless, no unequivocal systemic risk factors for the onset or progression of OA have been identified. Recently, there has been a growing interest in the biomechanical factors associated with the pathogenesis of OA. This review aims to discuss several of the more pertinent biomechanical and neuromuscular factors, such as the knee adduction moment and muscle strength, that are becoming increasingly accepted as factors that contribute toward the pathogenesis of knee OA.