The emetic response is primarily a protective reflex occurring in a wide variety of vertebrates in response to the ingestion of toxic compounds. The role of the nuclei in the brainstem, including the area postrema, nucleus tractus solitarius, the dorsal motor nucleus of the vagus, and the central pattern generator for vomiting, as well as the involvement of the abdominal visceral innervation relevant to the emetic reflex, have all been discussed by many researchers. The introduction of serotonin 5-HT(3)-receptor antagonists into clinical practice allowed for a dramatic improvement in the management of vomiting. However, vomiting still remains a significant problem. The mechanism of the emetic response is even more complicated than was first thought. This review attempts to bring together some of the evidence suggesting the roles of substance P and its receptor, neurokinin NK(1) receptor, in the brainstem nuclei in the development of emesis. Accordingly, NK(1)-receptor antagonists might represent novel drugs for the management of major types of emesis.