This review highlights some of the research advances in anaphylaxis and hypersensitivity reactions to foods, drugs, and insects and in allergic skin disease that were reported primarily in the Journal in 2006. Advances in diagnosis include identification of food proteins to which IgE binding is associated with severe reactions; elucidation of diagnostic relationships of skin prick test wheal size with outcomes of egg, tree nut, and sesame allergy; evaluation of the diagnostic utility of atopy patch testing for food; and the observation that yellow jacket sting outcomes are influenced by species. Mechanistic observations include the following: heating of birch pollen-related foods disrupts IgE binding but not T-cell epitopes; a simple imbalance of T(H)1/T(H)2 response does not explain variations in clinical expression of peanut allergy; and elucidation of the role of dendritic cells in drug hypersensitivity. With regard to treatment, a rapidly disintegrating epinephrine tablet showed promise for sublingual treatment of anaphylaxis, RNA interference techniques showed promise in creating lower-allergenic foods, and anti-IL-5 showed promise for treatment of eosinophilic esophagitis. Progress in our understanding of the immunology and the etiology of skin barrier dysfunction in atopic dermatitis has also been made. These observations will likely contribute toward optimizing management of these common allergic disorders.