Anaphylaxis has usually been studied and understood from an immunological view and the main lethal effects involve the cardio-vascular system. Despite exhaustive efforts exerted in this area of research, much more investigation is needed to mitigate, recognize or prevent this disease. The scope of this Research Topic is to present and discuss the current knowledge of anaphylaxis, from the clinic to the underlying molecular mechanisms. We are thankful to the medical doctors, researchers, and colleagues who have contributed to this issue, as it would not have been possible without their highly valuable expertise in allergy and anaphylaxis research.