Genome sequencing is leading to the discovery of new genes at a rate 50-100 times greater than that achieved by classical genetics, but the biological function of almost half of these genes is completely unknown. In order fully to exploit genome sequence data, a systematic approach to the discovery of gene function is required. Possible strategies are discussed here in the context of functional analysis in the yeast Saccharomyces cerevisiae, a model eukaryote whose genome sequence will soon be completed.