Osteoarthritis (OA) of the knee joint is a common cause of disability. This review presents the current evidence and knowledge regarding the genetic inheritability of OA of the knee, and a contemporary hypothesis for progression of the disease. The current evidence would suggest there is a hereditary predisposition to OA of the knee. However, this would seem to be multifactorial and the development of OA in the knee may depend upon multiple genetic factors, not only of those relating to cartilage degeneration but also of those relating to the morphology of the knee joint, both of these factors seem to be influenced by similar genes. Knowledge of these genes that affect the initiation and/ or progression of knee OA are important for development of new treatment options at an early stage of the disease preventing future physical disability.