The N К1 receptor is a G protein-coupled, seven transmembrane receptor. The gene and mRNA encoding the NK1 receptor have been cloned from several species. Substance P is the natural high-affinity ligand for this receptor. The receptor desensitizes then gradually resensitizes following repeat substance P exposure. The NK1 receptor is displayed extensively throughout the body. It appears prominently in various regions of the brain, spinal cord, lungs, and intestines. It is expressed on neurons, vascular endothelium, intestinal epithelium, lymphocytes and other cell types of the immune system. In the immune system, various cytokines as well as T cell receptor engagement can induce NK1 expression. Stimulation of the NK1 receptor excites several distinct intracellular second messenger systems. Activation of the receptor affects immunoregulation, cardiorespiratory physiology, neurotransmission, and intestinal secretion and absorption. It also influences neuronal survival and helps regulatethe emetic reflex, various behavioral responses, vascular dilatation, and vascular permeability. There are several nonpeptide NK1 receptor antagonists undergoing clinical evaluation for management of emesis, depression, and other pathophysiological processes.