Arthritis is characterized by pain and inflammation. Recently, attention has been focused on nerve-growth factor (NGF), a neurotrophin that is a key regulator of peripheral nociception because it mediates overexpression of proinflammatory neuron-derived molecules such as substance P, serotonin, and calcitonin gene-related peptide. Antibodies have been generated for NGF and its receptor that are effective in reducing pain in preclinical pain models, and clinical trials in patients with advanced knee and hip osteoarthritis and low-back pain. Results show pain reduction is rapid and sustained. Adverse events with anti-NGF included transient paraesthesia and edema, rapidly progressive OA, and, in a small number of patients treated with both anti-NGF and nonsteroidal anti-inflammatory drugs, osteonecrosis. Inhibition of the NGF-stimulated nociceptive pathway seems to be effective; however, the adverse effects require further investigation.