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Abstract: Genes are widely assumed to play a major role in the epidemiology of complex chronic diseases, yet attempts to characterize the genetic architecture of such traits have been frustrating. Understanding that evolution works by screening phenotypes rather than genotypes can help explain the source of this frustration. Complex traits are usually the result of long-term, often subtle, gene-environment interactions, such that individual life histories may be as important as population histories in predicting and explaining these traits. Recognizing that the problem is not due to technological limitations can help temper expectations and guide the design of future work in biomedical genetics, by allowing us to focus on better approaches where they exist and on those problems most likely to yield a genetic solution. We may even be forced to re-conceive complex biological causation.