This chapter looks at the toxicological hazard and exposure issues emanating from the use of engineered nanomaterials in food. A number of concerns have been raised over the safety of insoluble and biopersistent nanoparticles to human health and the environment. In this regard, there is emerging evidence in literature to suggest that, due to extremely small size, free nanoparticles are capable of penetrating biological membranes. This adds a new dimension to particle toxicology as nanoparticles may reach those targets in the body that are protected by barriers against the entry of larger particulate materials. However, much of the currently available toxicological evidence relates to inhalation exposure and studies on oral intake of engineered nanoparticles have only just started to emerge. Many of the reported effects have been derived from in vitro assays, or at very high doses. The current unavailability of validated methodologies for detection and characterisation of nanoparticles in complex food matrices poses further difficulties in the assessment of exposure to nanoparticles via consumption of nanofoods. The chapter suggests possible strategies for toxicological evaluation of nanoparticles, and stresses the need for tests that are carried out over prolonged exposures and are followed by histopathological investigations on multiple organs.