Anaphylaxis is a severe, potentially life-threatening allergic reaction that can occur through both IgE- and non-IgE-mediated pathways. The classic IgE-mediated pathway involves allergen-specific IgE binding to FcεRI on mast cells and basophils, triggering degranulation and the release of inflammatory mediators. Non-IgE-mediated mechanisms, which are commonly associated with drug-induced reactions, at least in mice, involve the activation of the G-protein-coupled receptor (MRGPRX2), triggering mast cell degranulation in an IgE independent manner. Anaphylaxis can also be mediated through IgG immune complex interaction with Fc gamma receptors on various cell types, leading to mediator release. This review will describe current understanding of the pathomechanisms of anaphylaxis. Understanding these diverse pathways is crucial for accurate diagnosis, effective treatment, and prevention of anaphylaxis.