Antiemetic drug selection depends on efficacy, cost, safety, and ease of dosing. Safety concerns have arisen regarding the side effects of antiemetics, specifically their effect on the ECG with prolongation of the QTc interval by the butyrophenones and the first-generation 5-HT3 receptor antagonist class of antiemetics. The impact of pharmocogenetics on antiemetic drug metabolism and their resulting efficacy has been correlated with genetic makeup affecting drug response. New antiemetic medications have added to our understanding of the peripheral and central nervous system (CNS) receptors and receptor antagonists targeting nausea and vomiting. These have included the second-generation 5-hydroxytryptamine-3 (5-HT3) antagonist [palonosetron] and the class of neurokinin-1 (NK-1) receptors and NK-1 receptor antagonist (aprepitant )The long half-life (40 h) of these medications offer an alternative method for the prophylaxis and/or treatment of PONV and postdischarge nausea and vomiting (PDNV). An analysis of ambulatory surgery patients has estimated that PDNV occurs with an incidence of approximately 30 %. In conclusion PONV is common after surgery, occurring in up to 70–80 % of high-risk patients who did not receive prophylactic antiemetics. PONV and PDNV are associated with morbidity and increased healthcare costs. Patient-specific, anesthesia- and surgery-related PONV and PDNV risk factors should be evaluated to determine the appropriate antiemetic therapy for proper prophylaxis or treatment.