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The study by Clarke et al., designed to examine whether sugammadex might attenuate rocuronium-induced anaphylaxis, appears to conclude prematurely that ‘sugammadex is unlikely to modify significantly the clinical course of an established allergic reaction’ [1]. There have been at least six reports (references available from author) of apparent mitigation, from five countries. Before the introduction of sugammadex, the capacity to remove an allergen from the circulation so easily did not exist, and the implications for the future of allergy management with inclusion complexes (not just for rocuronium) are significant. Within the presently accepted understanding of allergic mediator release, it is difficult to understand how sugammadex could so quickly alleviate anaphylactic symptoms [2]. However, as well as the classical pathway involving IgE and its high-affinity receptor FcεRI, we are just beginning to understand some mast cell activation pathways and effector mechanisms, for example, identification of an alternative pathway mediated by IgG, FcγRIII, macrophages and platelet activating factor (PAF), and the previously unsuspected importance of nitric oxide, endothelial nitric oxide synthase, PAF, PI3K/Akt signalling, cytokines IL-4 and IL-13, sphingosine-1-phosphate and sphingosine kinases [3-5]. In addition, there is still much to learn about sugammadex. How, for example, does the drug interact with mast cells? Degranulation is a rapid process leading to release of potent mediators that increase capillary permeability (wheal) and vasodilation (flare). Histamine liberation and increased local blood flow begins within two minutes of allergen challenge and up to 50% of wheal size cannot be explained by histamine alone [6, 7]. Any anti-anaphylactic effects of sugammadex, therefore, may not be seen if researchers were only to analyse cutaneous signs. There is a considerable amount of further research to be done before it can be so readily concluded that sugammadex’s potential for modifying an established allergic reaction to rocuronium can be discounted.