The galactose-alpha-1,3-galactose (alpha-Gal) syndrome is a newly recognized and unique form of food allergy, characterized by delayed reactions to mammalian meats. This form of allergy occurs in individuals who become sensitized to alpha-Gal, a carbohydrate that is present on most mammalian tissues. Sensitization occurs after exposure to multiple arthropod bites, most commonly the lone star tick. Cases of the alpha-Gal syndrome are primarily found in the southeastern United States, which overlaps with the known geographic distribution of the lone star tick. Patients present with a history of delayed symptom onset, ∼2‐6 hours after ingestion of mammalian meat. As with other immunoglobulin E (IgE) mediated food allergic reactions, alpha-Gal reaction symptoms may include skin, respiratory, gastrointestinal, or cardiovascular systems, and severity may range from mild reactions to severe anaphylaxis. The diagnosis is based on the detection of alpha-Gal specific IgE (sIgE) as well as the total IgE value because some cases include patients with low total IgE levels but a high percentage of alpha-Gal sIgE to total serum IgE levels. Percutaneous testing with commercial meat skin-prick testing extracts is not a reliable tool for diagnosis. Prick-prick skin testing to fresh cooked meat may be considered, whereas intradermal testing to fresh meat is primarily reserved for research purposes. The mainstay of treatment involves avoidance of mammalian meat and medications that express the same carbohydrate antigen. With a small portion of patients, other meat-containing products should also be avoided if symptoms persist with mammalian meat avoidance alone. Prolonged avoidance of mammalian meat as well as avoidance of further tick bites can decrease alpha-Gal sIgE over time, and some patients are able to reintroduce mammalian meat into their diet.