A contributing role of nerve growth factor (NGF)-mediated neuroimmunologic mechanisms has provided a new dimension in the understanding of various cutaneous and systemic inflammatory diseases. Recent evidence implicates NGF as a key mediator of inflammation and pain. NGF influences an inflammatory reaction by regulating neuropeptides, angiogenesis, cell trafficking molecules, and T cell activation. All of these functions of NGF are relevant in maintenance or initiation of the critical biologic events in various rheumatologic conditions. The recognition of a pathologic role of NGF and its receptor system has provided an attractive opportunity to develop a novel class of therapeutics for inflammatory diseases and chronic pain syndromes. In this chapter we will discuss the role of NGF and its receptor system in psoriatic disease, inflammatory arthritis, and arthritic pain of osteoarthritis.