OA represents the final common pathway of a number of pathologic processes. The challenge is to define and classify the subsets of OA to understand the causes and to devise specific therapies. Effective chondroprotective therapies will be most useful when applied to high-risk individuals before the emergence of symptomatic OA. This will be feasible only with an improved understanding of the complex interaction of genes and environment in the OA disease process. Moreover, identifying the heritable bases of this disease will provide insight into the molecular mechanisms of the complex pathway that results in OA. Clinicians who encounter and treat OA patients can look forward to the development of more effective and innovative therapies based on a rapidly improving understanding of OA.