Chemotherapy-induced nausea and vomiting (CINV) remains one of the most challenging adverse events of chemotherapy, and one that has substantial negative effects on patients, clinicians, and the wider health care system. Use of CINV prophylaxis consistent with clinical practice guidelines is essential for attaining optimal CINV control. In recent years, there has been a dramatic improvement in the control of CINV with the introduction of effective antiemetic agents, including the serotonin (5-hydroxytryptamine [5-HT3]) receptor antagonists (ondansetron, granisetron, and palonosetron) and the neurokinin-1 (NK1) receptor antagonists (aprepitant and fosaprepitant). An important benefit of the newer antiemetic agents is their improved ability to control the delayed CINV that can develop in the days after chemotherapy administration. In October 2014, a fixed-dose oral combination containing the novel NK1 receptor antagonist netupitant and palonosetron (NEPA) received approval from the US Food and Drug Administration. The combination of 2 effective antiemetic agents in a single, oral capsule may help simplify CINV management. Ongoing studies are evaluating new CINV approaches (eg, the novel NK1 receptor antagonist rolapitant), as well as the optimal use of existing therapies. Patient education regarding the timing, prevention, and treatment of CINV is another key component of CINV management.