This article focuses on pain associated with osteoarthritis (OA). It first describes the basic biology of articular cartilage and other joint structures and the defining features of the osteoarthritic disease process. Subsequently, the possible origins of pain in OA are discussed before embarking on how to manage this clinical entity. The emphasis is on the pharmacologic management of joint pain, and attention is paid to systemic therapeutic strategies as well as to local (intra-articular) treatment modalities. Nonmedical ways of modulating joint pain are briefly mentioned, but not extensively discussed, as these are outside the scope of this article.