Purpose of ReviewThe alpha-Gal (-Gal) syndrome is characterized by the presence of IgE antibodies directed at the carbohydrate galactose-alpha-1,3-galactose (-Gal). In this article, we review the presence of -Gal in food and non-food sources; we discuss the evolutionary context of the antibody response to -Gal and highlight immune responses to -Gal and other carbohydrates.Recent findingsIgE antibodies have been associated with delayed allergy to red meat. In addition to food, drugs, and other products of animal origin are increasingly perceived as a risk for patients sensitized to -Gal. The link between tick bites and anti--Gal IgE-antibody production that has been established first by epidemiological studies has now been confirmed in mouse models.SummaryThe anti--Gal immune response is complex and characterized by a unique feature. IgM and IgG antibodies have been found to confer protection against pathogens whereas the IgE-response to -Gal is detrimental and causes severe reactions upon exposure to mammalian meat and other products.