Chemotherapy-induced nausea and vomiting (CINV) are among the most feared side effects of cancer treatment. With increasingly more complex chemotherapy treatments, CINV plays an important role in determining patients' quality of life, as well as when to halt potentially lifesaving therapy. Although significant progress has been made in the treatment of CINV, patients undergoing chemotherapy continue to report that this side effect is persistent and distressing. In 2003, two new agents were added to the armamentarium of antiemetic therapy. The U.S. Food and Drug Administration approved palonosetron, a longer-acting serotonin antagonist, and aprepitant, a neurokinin-1 antagonist and the first in a new class of antiemetics, for the treatment of CINV. Although the indications for both agents are similar, they have distinct differences. Decisions regarding placement of these agents into existing antiemetic protocols can be based on national guidelines, review of the literature, and clinical experience. This article will review current antiemetic therapy with an emphasis on the new additions to the treatment of CINV. Aprepitant and palonosetron represent significant changes in the treatment of CINV. Oncology nurses need to know current approaches to maximize effective antiemetic therapy.