Welcome to our special issue on Human Genetics and Disease, which we are publishing in celebration of the second anniversary of Nature Reviews Genetics and making freely available online this month at http://www.nature.com/nrg/ (for more on this topic, see our web focus at http://www.nature.com/nrg/focus/humgen).

We hope that this special issue provides you with a snapshot of some of the key challenges that are currently facing the field of human genetics and of the progress that is being made in tackling them. Foremost among these is how to elucidate the genetic basis of multigenic disease. One possible approach to studying such diseases is discussed in the highlight on p729, which describes the combined use of several methods to investigate the complex disorder Hirschprung disease. In their review, Jose Badano and Nicholas Katsanis (p779) also discuss the tools and approaches that are being used to detect and dissect oligogenic diseases. They argue that — owing to the increasing realization that many monogenic disease traits are in fact caused by the sum effects of defects at several loci — it is perhaps time to rethink the way in which we describe the transmission of genetic diseases. Of course, identifying a disease gene is just the first step towards understanding a disease's aetiology. Both David Lomas and Robin Carrell (p759) and Hagop Youssoufian and Reed Pyeritz (p748) discuss two different disease-causing molecular mechanisms — disrupted protein folding and somatic mosaicism, respectively.

Not all of the challenges that face human geneticists are biological in nature. In her article, Lori Andrews presents evidence of the negative impact that gene patents are having on the pace and culture of genetic research and on the provision of clinical genetic services, and argues strongly in favour of reforming the gene-patenting system.