The recently completed genome sequence of the model plant species Arabidopsis has been estimated to encode over 25,000 proteins, which, on the basis of their function, can be classified into structural and metabolic (the vast majority of plant proteins), protective proteins, which defend a plant against invasion by pathogens or feeding by pests, and storage proteins, which proved a nutrient store to support germination in seeds. It is now clear that almost all plant food allergens are either protective or storage proteins. It is also becoming evident that those proteins that trigger the development of an allergic response through the gastrointestinal tract belong primarily to two large protein superfamilies: (1) The cereal prolamin superfamily, comprising three major groups of plant food allergens, the 2S albumins, lipid transfer proteins, and cereal alpha-amylase/trypsin inhibitors, which have related structures, and are stable to thermal processing and proteolysis. They include major allergens from Brazil nut, peanuts, fruits, such as peaches, and cereals, such as rice and wheat; (2) The cupin superfamily, comprising the major globulin storage proteins from a number of plant species. The globulins have been found to be allergens in plant foods, such as peanuts, soya bean, and walnut; (3) The cyteine protease C1 family, comprising the papain-like proteases from microbes, plants, and animals. This family contains two notable allergens that sensitize via the GI tract, namely actinidin from kiwi fruit and the soybean allergen, Gly m Bd 30k/P34. This study describes the properties, structures, and evolutionary relationships of these protein families, the allergens that belong to them, and discusses them in relation to the role protein structure may play in determining protein allergenicity.