Proteins encoded by mobile genetic elements occasionally assume cellular roles. Telomerase, for example, is a reverse transcriptase that replicates chromosome ends, and Rag1 is a transposase that mediates immunoglobulin gene rearrangements. In this article, we report cellular genes related to integrases that are not associated with a retrovirus or retrotransposon. These integrases are found in diverse eukaryotes and are evolving under functional constraint. We propose that the cellular integrases have assumed a host role and, like their retroelement counterparts, probably function in DNA metabolism.