For sequence analysis, one genome may be good, but two genomes are better, and with three or more you have a bioinformatics bonanza — at least judging by the talks at the Genome Informatics conference at Cold Spring Harbor Laboratory earlier this month. Not only did researchers show how they are applying existing bioinformatics tools to multiple genomes in order to gain more insight into biological function, but it was clear that comparative genomics is providing the impetus for a new generation of sequence analysis tools to speed the process.