If you've ploughed your way through the recent issues of Nature and Science, you might be suffering from a condition known as genome fatigue. Symptoms include hyperbolic tendencies, speaking in metaphors and having trouble finishing anything.

So, in the interests of our readers' health, you will find the usual mix of exciting genetics and genomics in this issue of Nature Reviews Genetics . Sex features quite heavily — Bruce Lahn and colleagues review the evolutionary history of the human Y chromosome, and David Zarkower considers diversity and conservation in the mechanisms of sex determination. In his wide-ranging review, Joe Nadeau draws together a collection of phenomena that come under the umbrella of genetic modifiers in mammals, and in Perspectives, Hank Greely reminds us of the other genome project — the Human Genome Diversity Project — and the issues it raises.

We would not for one instant suggest that the publication of the (draft) human sequence is anything other than a singular landmark in human endeavour — and a complimentary copy of the 15 February issue of Nature will be provided to our subscribers. Witness also the reaction of the world's press to the event, as covered this month in Highlights. The repercussions of this achievement will be seen in our pages over the coming months. Later in the year, you will find articles on genome sequencing strategies, segmental duplications and disease, genome evolution, genome annotation and plenty more. But these will have to wait. For now, look at this issue as the antidote to genome fatigue.