Aprepitant (Emend, Merck Inc., Whitehouse Station, NJ), a neurokin-1 (NK1) receptor antagonist, is a first-in-class agent approved for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). It competitively binds to NK1 receptors, blocks the binding of substance P, the natural ligand, and prevents signal transduction. Early clinical trials showed that aprepitant combined with standard therapy (corticosteroids and serotonin receptor antagonists) provided improved antiemetic protection in patients receiving highly emetogenic chemotherapy. The results of three randomized, double blind, placebo-controlled trials that compared aprepitant plus standard therapy with standard therapy plus placebo showed significant improvements in complete response rates (defined as no emesis and no use of rescue medication) with the addition of aprepitant (58.8% to 71% vs. 43.3% to 52.3%; P < .05 for all). Benefits were found in the acute phases, delayed phases, and in the overall study periods. Multiple secondary endpoints also favored the addition of aprepitant, particularly in the delayed phases and overall study periods. In extended trials in which treatment was continued for up to 6 cycles of highly emetogenic chemotherapy, the antiemetic effect was maintained and remained statistically greater for the aprepitant plus standard therapy group compared with standard therapy and placebo. The addition of aprepitant was well tolerated, and common adverse events were similar to those seen with standard therapy plus placebo. A clinically significant drug interaction with CYP3A4-metabolized cytotoxic agents was reported in one trial, but not confirmed in the others. The additional protection confirmed by aprepitant translated into a decreased impact of CINV on patients' daily lives as measured by the Functional Living Index-Emesis questionnaire. Aprepitant adds additional antiemetic protection to standard therapy and should be considered in all patients receiving highly emetogenic chemotherapy.