The eukaryotic homologues of the Escherichia coli RecQ DNA helicase play conserved roles in the maintenance of genome stability. Results obtained in yeast and mammalian systems are beginning to form a coherent picture about what these helicases do to ensure normal cell division and why humans who lack these enzymes are cancer prone. Recent data suggest that the yeast enzyme Sgs1p, as well as two human homologues, which are encoded by the Bloom's and Werner's syndrome genes, function during DNA replication and possibly in a replication checkpoint specific to S phase.