Osteoarthritis (OA) is the most prevalent form of arthritis in the elderly. A large body of evidence, including familial aggregation and classic twin studies, indicates that primary OA has a strong hereditary component that is likely polygenic in nature. Furthermore, traits related to OA, such as longitudinal changes in cartilage volume and progression of radiographic features, are also under genetic control. In recent years, several linkage analysis and candidate gene studies have been performed and have unveiled some of the specific genes involved in disease risk, such as FRZB and GDF5. The authors discuss the impact that future genome-wide association scans can have on our understanding of the pathogenesis of OA and on identifying individuals at high risk for developing severe OA.