Stoevesandt J, et al. - Ranking of Hymenoptera venom allergy among the top three causes of anaphylaxis worldwide, and classification of approximately one-quarter of sting-induced reactions as severe led researchers to analyze the current knowledge about risk factors and indicators of severe or fatal anaphylactic sting reactions and assist in recommendation regarding the initiation or discontinuation of venom immunotherapy and/or the prescription of epinephrine auto-injectors. Major unmodifiable long-term risk factors were systemic mastocytosis and senior age that may reinforce the indication for venom immunotherapy. The risk of severe or even fatal reactions increases in correlation to vespid venom allergy and male sex. Justification for recommendations to discontinue guideline-directed antihypertensive treatment could not be provided in view of the inconclusive available data regarding potential effects of beta-blockers and/or ACE inhibitors in coexisting venom allergy. During sting-induced anaphylaxis, the absence of urticaria/angioedema is suggestive of a severe reaction, serum tryptase elevation, and mast cell clonality. In Hymenoptera venom-allergic patients, basal serum tryptase levels are determined for risk assessment. Measuring the activity of the platelet-activating factor acetylhydrolase is a supplementary strategy but is not accessible for routine diagnostic use.