Chemotherapy-induced nausea and vomiting (CINV) remains a significant detriment to patient quality of life and a major impediment to successful delivery of chemotherapy. CINV is generally categorized in three phases: acute (0-24 hours post treatment), delayed (24-120 hours post treatment), and anticipatory. Two agents represents an important step forward in the clinician's ability to control CINV. Palonosetron, a serotonin-receptor antagonist, and aprepitant, a neurokinin-1 receptor antagonist, have both shown efficacy in combating emesis in the acute and delayed phases; since these two agents are of different drug classes, there is the potential for augmented antiemetic efficacy when the two are used together, as shown in a recent phase III trial. Challenges remain in the prevention of CINV, such as improved detection, the development of clinically useful assessment tools, and the revision of treatment guidelines.