Objective: To present an up-to-date synopsis on the global prevalence, natural history, nature of allergens, and immune mechanisms of sesame allergy. Data Sources: We performed a literature search using the PubMed database. We obtained information on regulatory issues from the Web pages of respective agencies. Study Selection: The PubMed search was performed using the algorithm sesame AND allergy. Date restriction was not used, and only articles in English were considered. The articles obtained were screened for additional references to work not obtained in the initial search. Each article was analyzed, and a pooled source of published information was generated. Results: Evidence was found for increased reporting of sesame allergy during the past 5 decades, with reports mostly from developed countries. Clinically, most sesame allergy was presented in at least 2 major forms: (1) immediate hypersensitivity, often expressed as systemic anaphylaxis, associated with positive skin prick test and/or IgE antibody test results to sesame proteins with some cross-reactivity with other foods, and (2) delayed hypersensitivity to lignin-like compounds in sesame oil clinically expressed as contact allergic dermatitis. There were a few cases of immediate hypersensitivity to sesame with negative skin prick test and/or IgE antibody test results that were confirmed by oral challenge tests. Conclusions: Sesame allergy is a significant, serious, and growing problem. Evidence exists of the ability of protein and oil components of sesame to trigger immediate hypersensitivity via IgE antibody and delayed hypersensitivity via cell-mediated immune responses, respectively.