The bioavailability (utilization) of trace elements is very variable, depending on the characteristics of the element itself, composition of the diet, gastrointestinal conditions and other physiological factors. To derive dietary recommendations and make use of emerging information on diet-gene interactions relating to nutritional requirements for trace elements, methods for assessing bioavailability are required. The trace elements of particular interest include iron, zinc, selenium and copper because of problems of deficiency, purported links with chronic diseases, and the growing market in fortified foods and supplements. The absorption and subsequent metabolism of trace elements can be monitored using stable isotope tracers, but there are difficulties associated with this approach. Although radioisotopes offer many advantages over stable isotopes, their use is restricted due to safety and ethical issues. The difficulties and limitations of methodologies associated with labelling of trace elements in foods with stable isotopes, design of human studies to generate results that predict bioavailability, and detection and quantification of stable isotopes in biological samples are discussed.