With no disease-modifying osteoarthritis drugs on the immediate horizon, the goal of osteoarthritis therapy remains management of pain and maintenance of function. Evidence supports use of nonpharmacologic measures including patient education, judicious exercise and weight loss, and assistive devices when appropriate to reduce pain and further loss of function. First line pharmacotherapy is acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs). However, toxicities are associated with long-term use of these drugs. Evidence also supports the use of opioids in osteoarthritis pain management when other interventions are insufficient. NSAIDs and opioids are mutually dose sparing and combining relatively low doses of a drug from each class provides synergistic analgesia while limiting toxicity. Alternative therapies include tramadol and intra-articular injections of steroids and hyaluronic acid. There is evidence to support glucosamine as an adjunct in treating osteoarthritis. Evidence is lacking to support the use of chondroitin, S-adenosyl-methionine, or dimethyl sulfoxide in osteoarthritis pain management.