The bakers' yeast, Saccharomyces cerevisiae, a microorganism of major importance for bioindustries, and one of the favored model organisms for basic biological research, is the first eukaryote whose genome is entirely sequenced. Beyond the wealth of novel biological information, it is the extent of what remains to be understood in the genome of a simple unicellular organism that is the most striking result: a significant proportion of yeast genes are orphans of unpredictable function. Offering the possibility of large-scale reverse genetics, yeast will be a powerful model for post-sequencing studies. But geneticists are now faced with the difficulty of asking novel questions.