Chemotherapy-induced nausea and vomiting (CINV) is a common and serious problem encountered by many patients receiving anticancer therapy. Up to three fourths of all cancer patients experience chemotherapy-related emesis. Risk factors include specific chemotherapeutic agents used, female gender, age less than 50 years, and history of nausea or vomiting. Since CINV can complicate or prevent administration of planned therapy, decrease quality of life, and increase healthcare costs, its effective management is essential. Although serotonin receptor antagonists have significantly improved outcomes, next-generation analogs such as palonosetron have shown greater specificity and increased efficacy. Novel agents like the neurokinin-1 receptor antagonist aprepitant are also active, particularly when combined with palonosetron and dexamethasone. In recent years, the greatest advances have been made in the prevention of vomiting (especially acute vomiting), although uncontrolled nausea is still a major concern for many patients. Better treatments are needed for management of delayed CINV and for patients who do not respond to standard antiemetic therapies.