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 Saccfiaromyces cerevisiae, a model eukaryote whose genome sequence will soon be completed.