Despite major advances, emesis remains a major problem in the context of cancer chemotherapy and in the postoperative period. A better understanding of the relevant neurocircuitry, especially the central pattern generator responsible for emesis and the central role of substance P, led to the development of a new class of antiemetics: the neurokinin-1 (NK1) receptor antagonists. Aprepitant is the first NK1 receptor antagonist approved for use in postoperative nausea and vomiting, but several other compounds are currently being investigated for their potential as antiemetics in the postoperative and cancer chemotherapy settings.