Whenever official approval for the introduction of genetically modified (GM) foods has been given in Europe or the United States, regulatory committees have invoked the concept of 'substantial equivalence'. This means that if a GM food can be characterized as substantially equivalent to its 'natural' antecedent, it can be assumed to pose no new health risks and hence to be acceptable for commercial use. At first sight, the approach might seem plausible and attractively simple, but we believe that it is misguided, and should be abandoned in favour of one that includes biological, toxicological and immunological tests rather than merely chemical ones. The concept of substantial equivalence has never been properly defined; the degree of difference between a natural food and its GM alternative before its 'substance' ceases to be acceptably 'equivalent' is not defined anywhere, nor has an exact definition been agreed by legislators. It is exactly this vagueness that makes the concept useful to industry but unacceptable to the consumer. Moreover, the reliance by policymakers on the concept of substantial equivalence acts as a barrier to further research into the possible risks of eating GM foods.