Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. 5-hydroxytryptamine-3 (5-HT3) receptor antagonists plus dexamethasone have significantly improved the control of acute CINV, but delayed CINV remains a significant clinical problem. Two new agents, palonosetron and aprepitant, have been approved for the prevention of both acute and delayed CINV. Palonosetron is a second-generation 5-HT3 receptor antagonist with a longer half-life and a higher binding affinity than first-generation 5-HT3 receptor antagonists. Aprepitant is the first agent available in the new drug class of neurokinin-1 (NK-1) receptor antagonists. Casopitant is another NK-1 receptor antagonist that is under review by the FDA after recent completion of Phase III clinical trials. The introduction of these new agents has generated revised antiemetic guidelines for the prevention of CINV. Future studies may consider the use of palonosetron, aprepitant and casopitant with other antiemetic agents (olanzapine, gabapentin, cannabinoids) in moderately and highly emetogenic chemotherapy, as well as in the clinical settings of multiple-day chemotherapy and bone marrow transplantation. © 2009 Informa UK Ltd All rights reserved.