Osteoarthritis represents a major therapeutic challenge to medical and health-care providers. In part, this is related to the limited tools that are available for assessing the structural state of joint tissues and to the lack of effective therapies to alter the natural history of osteoarthritis progression. From a clinical and pathologic perspective, osteoarthritis is not a homogeneous disorder, and the underlying pathogenic mechanisms differ among individuals. Even in the same individual, the pathologic processes and etiologic mechanisms may differ at specific stages of disease progression. In the development of strategies for effective intervention, several issues need to be considered. First, the stage of osteoarthritis progression must be considered. Therapies that are effective prior to the development of structural alterations may have limited utility in later stages. Similarly, treatments for late-stage osteoarthritis need to be adapted and adjusted to target specific symptoms that are amenable to modification. Despite the limited therapeutic options available for the treatment of osteoarthritis, there are interventions that have been shown to be beneficial. These include preventive strategies as well as specific interventions, such as the judicious use of analgesic medications for the control of pain. It is essential to develop an integrated multidisciplinary approach to osteoarthritis; this approach should be one that involves medical and surgical specialists as well as other health-care providers. In addition, further clinical and basic-science research is needed so that improved and more effective therapies for osteoarthritis as well as better methods for monitoring and assessing the efficacy of treatment interventions can be developed.