Endocrine disrupters (ED) are a heterogeneous group of chemicals including persistent contaminants, pesticides, as well as compounds present in consumer products and natural substances. For most ED, the food chain is a current major exposure route for the general population. ED can enter the food chain through the living environment (e.g., feeds, fertilizers) of food-producing organisms, be directly employed in food production (e.g., pesticides) or be released from food contact materials (such as bisphenol A or phthalates); in addition, the endocrine disruption potential of some natural compounds in edible plants, including the so-called phytoestrogens, should not be overlooked. An exposure assessment has to consider the specific liability of food commodities to contamination with specific ED (e.g., polychlorinated and polybrominated chemicals in lipid-rich foods). The paper discusses the main toxicological research issues in order to support the risk assessment of ED in food chains, including: the potential for additive, ‘cocktail' effects (as from multiple pesticide residues); the long-term effects on target body systems (e.g., reproductive, nervous) elicited by exposure during prenatal as well as postnatal life stage windows, and toxicant/nutrient interactions (e.g., thyroid-targeting ED and iodine status). Food safety systems should exploit the available knowledge to improve prevention of long-term risks along the whole food chain.