One of the driving forces that push forward the boundaries of genetic research is the desire to understand, treat and prevent inherited human disease. This relationship also works the other way round, with new ways of thinking in genetics colouring the way we view hereditary disease.

An article by David Patterson and Alberto Costa (page 137) provides a classic example of the intertwined histories of human genetics and disease. This Timeline — part of our History of Genetic Disease series — charts how our understanding of Down syndrome has developed from the time that Mendel first put forward his theories of inheritance to more recent advances in transgenic technologies. The molecular basis of the disease is beginning to come into focus, and new 'omics' technologies promise to bring new insights in the future.

But understanding diseases such as Down syndrome that have relatively simple patterns of inheritance is far from the whole story. The vast majority of human genetic disease results from a complex mixture of inherited and environmental factors, and tackling these disorders presents a new set of challenges to human geneticists.

Two Reviews in this issue — by Joel Hirschhorn and Mark Daly (page 95) and William Wang and colleagues (page 109) — discuss an approach that has great potential to increase our understanding of complex genetic disease. Genome-wide association studies are poised to combine advances in our knowledge of human genome structure and population genetics, together with improvements in genotyping technology, to vastly improve our ability to pinpoint disease-associated variants. Both Reviews look forward to the first insights from these studies, which should tell us how far our current understanding of genetics can take us towards the ultimate goals of treating and perhaps preventing inherited human disease.