Purpose of Review The purpose of this review is to provide a better understanding of anaphylaxis pathophysiology and describe the underlying mechanisms, effector cells, and the potential biomarkers involved depending on the anaphylaxis endotypes. Recent Findings New insight into the potential relevance of pathways others than IgE-dependent anaphylaxis has been unraveled, as well as other biomarkers than tryptase, such as the role of platelet activation factor, basogranulin, dipeptidyl peptidase I, CCL-2, and other cytokines. Summary Gaining knowledge of all the mediators and cellular activation/communication pathways involved in each endotype of anaphylaxis will allow the application of precision medicine in patients with anaphylactic reactions, providing insights to the most appropriate approach in each case and helping to stratify severity and risk prediction.