Oral bioaccessibility, also known as in vitro gastrointestinal extraction or the physiologically based extraction test (PBET), is an important tool when assessing the risk to humans from persistent organic pollutants (POPs) (and metals). The approach seeks to mimic the processes of human food digestion and thereby assess the bioavailability of POPs (and metals) from materials consumed either accidentally or intentionally in the diet. In vitro conditions are created to simulate various actions in the stomach and intestines (although some methods also include the mouth compartment). This paper reviews the current status of oral bioaccessibility with respect to the release of POPs from soil and related samples of environmental importance. Particular emphasis is placed on the parameters that influence gastrointestinal extraction including gastric and intestinal pH, enzymes, bile salts, food constituents and residence time. In addition, important developments in the use of in vitro gastrointestinal extraction are highlighted. These developments include the use of epithelial Caco-2 cells to mimic the intestinal cell lining, the potential for biotransformation of POPs into estrogenic metabolites as a result of colon microbiota, and the use of in vivo studies to validate existing approaches.