Substance P is a neuropeptide that is released from sensory nerves and which has a number of pro-inflammatory effects. In this article, we review the evidence for a role of substance P in arthritis, both in experimental animal models and rheumatoid arthritis patients. Substance P expression is altered in the joint and dorsal horn of arthritic animals, exogenous substance P and neurokinin 1 (NK(1)) receptor antagonists modulate responses in the joint, and there is some evidence for a role of substance P in human joint disease. However, the therapeutic potential of NK(1) receptor antagonists in the treatment of rheumatoid arthritis remains controversial.