: The addition of neurokinin-1 receptor antagonists (NKRAs) to standard prophylaxis of 5-hydroxytryptamine-3 RA (5-HTRA) plus dexamethasone more effectively prevents chemotherapy-induced nausea and vomiting (CINV) associated with highly and moderately emetogenic chemotherapy. : This review presents the evidence base for the use of oral and intravenous (IV) NKRAs, focusing on the pharmacologic and clinical properties as a class, and highlighting differences between agents. A PubMed literature search was conducted from 2000 to 2018. : Adherence to international antiemetic guidelines remains a clinical challenge. Strategies to simplify antiemetic regimens and facilitate their administration may improve compliance and treatment outcomes. The use of fixed-combination antiemetics offers clinical utility, in combining an NKRA with a 5-HTRA in a single oral dose. The use of long-lasting NKRAs and administering CINV prophylaxis closer to the time of chemotherapy may also assist with guideline and treatment compliance, diminishing the need for home-based administration, and potentially reducing resource utilization. The availability of IV and oral formulations of NKRAs and NKRA-5-HTRA fixed combinations offers further utility, particularly for those patients unsuited for oral administration. However, safety considerations with respect to injection site toxicity and hypersensitivity reactions of the new NKRA IV formulations deserve close attention.