Pollinosis patients often display adverse reactions upon the ingestion of plant-derived foods as a result of immunoglobulin E (IgE) cross-reactive structures shared by pollen and food allergen sources. The symptoms of such pollen-food syndromes (PFS) or class 2 food allergies range from local oral allergy syndrome to severe systemic anaphylaxis. Two clinical syndromes, the celery-mugwort-spice syndrome and the mugwort-mustard-allergy syndrome have been described in association with weed pollinosis. However, other associations between weed pollinosis and hypersensitivity to certain kinds of food have also been observed, like the mugwort-peach, the ragweed-melon-banana, the plantain-melon, the pellitory-pistachio, the goosefoot-fruit, the Russian thistle-saffron, and the hop-celery association. The number of allergen sources involved, the allergens, and influencing factors including geography, diet, and food preparation contribute to the high clinical complexity of PFS. So far, known causative cross-reactive allergens include profilins, lipid transfer proteins, and high-molecular weight allergens and/or glycoallergens. The current usage of nonstandardized allergen extracts poses additional problems for both diagnosis and therapy of PFS patients. Further identification and characterization of involved allergens is inescapable for better understanding of PFS and vaccine development. Panels of recombinant allergens and/or hypo-allergens are promising tools to improve both PFS diagnostics and therapy.