Genetic epidemiology has greatly expanded its scope as a result of major technological innovations in the past decade. Laboratory capacity to determine DNA variation and archival information on the human genome sequence are now readily available. A wide range of research projects have been launched on chronic disease and health problems of aging, on the assumption that a better understanding of mechanisms will improve treatment and prevention. In many instances, the actions of genes are known to be modified by environmental conditions, and considerable emphasis has now been placed on finding specific interactions between genes and the environment. Studies in agriculture and animals provide clear empirical evidence on the importance of this concept. Describing gene-environment interactions in studies of humans is still very challenging, however, given the difficulties in study design and measurement. Despite the theoretical value of characterizing both intrinsic and extrinsic components of the causal process in the development of disease, the argument can also be made that main effects of each component separately are much more important. For these reasons, gene-environment interactions are likely to remain a conceptual framework for health research rather than a practical goal for the foreseeable future.