© 2018, The Author(s). Polysorbate 80 is a synthetic nonionic surfactant used as an excipient in drug formulation. Various products formulated with polysorbate 80 are used in the oncology setting for chemotherapy, supportive care, or prevention, including docetaxel, epoetin/darbepoetin, and fosaprepitant. However, polysorbate 80, like some other surfactants, is not an inert compound and has been implicated in a number of systemic and injection- and infusion-site adverse events (ISAEs). The current formulation of intravenous fosaprepitant has been associated with an increased risk of hypersensitivity systemic reactions (HSRs). Factors that have been associated with an increased risk of fosaprepitant-related ISAEs include the site of administration (peripheral vs. central venous), coadministration of anthracycline-based chemotherapy, number of chemotherapy cycles or fosaprepitant doses, and concentration of fosaprepitant administered. Recently, two polysorbate 80-free agents have been approved: intravenous rolapitant, which is a neurokinin 1 (NK-1) receptor antagonist formulated with the synthetic surfactant polyoxyl 15 hydroxystearate, and intravenous HTX-019, which is a novel NK-1 receptor antagonist free of synthetic surfactants. Alternative formulations will obviate the polysorbate 80-associated ISAEs and HSRs and should improve overall management of chemotherapy-induced nausea and vomiting. Funding Heron Therapeutics, Inc.