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. The use of a combination of a serotonin 5-HT(3) receptor antagonist, dexamethasone and a neurokinin 1 (NK(1)) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second-generation 5-HT(3) receptor antagonist with a different half-life, a different binding capacity and a different mechanism of action than the first-generation 5-HT(3) receptor antagonists appears to be the most effective agent in its class. Aprepitant, the first and only agent clinically available in the NK(1) receptor antagonist drug class has been used effectively as an additive agent to the 5-HT(3) receptor antagonists and dexamethasone to control CINV. Rolapitant and netupitant are other NK(1) receptor antagonists that are currently in phase III clinical trials. Despite the control of emesis, nausea has not been well controlled by current agents. Olanzapine, a US-FDA approved antipsychotic, has emerged in recent trials as an effective preventative agent for CINV, as well as a very effective agent for the treatment of breakthrough emesis and nausea. Clinical trials using gabapentin, cannabinoids and ginger have not been definitive regarding their efficacy in the prevention of CINV. Additional studies are necessary for the control of nausea and for the control of CINV in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.