Almost 15 years ago—April, 1992—Nature Genetics was launched as the first of the Nature research journals. Last year we were discussing ideas for commemorating this anniversary, following up on the ‘retrospective’ supplement that we published to celebrate ten years of NG (by the way, see here for an amusing take on the whole issue of anniversary issues). We decided on a more forward-looking theme this time, and stimulated by the brilliant annual questions that edge.org asks of its contributors and friends, we decided to launch our own ‘Question of the Year’. But what to ask? In the end, we decided on the topic of sequencing, given how much attention has been paid in recent months to technologies that may bring down the cost of sequencing substantially. What would geneticists actually do with all of this sequencing power? We’re asking this question to a select group, and the first 20 responses have been posted. An additional 5-10 replies will be posted every month until October, and we hope everyone finds them to be as provocative as we do.