As life expectancy increases every decade, the incidence and prevalence of osteoarthritis (OA) also will increase. Despite progress in our knowledge of the pathophysiology of OA, the management of OA-mediated pain continues to challenge physicians. Concern regarding the cardiovascular effects of cyclooxygenase-2 inhibitors and the gastrointestinal and renal side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in general has limited the use of these medications in the management of chronic non-cancer pain. Appropriately dosed and monitored use of opioids for OA pain, when more conservative methods have failed, has potentially fewer life-threatening complications associated with it than the more commonly and often less successfully employed pharmacotherapeutic approaches to care. When used as part of a multimodal approach to pain control, opioids are a safe and effective treatment for joint pain, including that of OA. Patients for whom NSAIDs are contraindicated, or for whom combined acetaminophen, tramadol, and NSAID therapy is ineffective, may be started on low-dose opioids and titrated as needed and tolerated. Patient education and informed consent, exercise, complementary medicine, and the use of a controlled substance agreement increases the likelihood of patient compliance with treatment guidelines, improving functional capacity and quality of life.