Anaphylaxis typically occurs due to immunological mechanisms involving IgE, IgG, or complement-mediated responses, but nonimmunological mechanisms can also contribute to the development of anaphylaxis by triggering mast cell and basophil degranulation. In cases where alternative treatment options are unavailable, or when the use of a specific drug is essential, a desensitization protocol should be considered. In this context, we present a successful oral desensitization protocol in a pediatric patient who experienced anaphylaxis after taking acetazolamide orally.