Over the last decade great investments have been made in the acquisition of enormous amounts of gene sequence data from a diverse collection of org- isms. Realizing the full potential of these investments will require the continued development of computational tools for comparative genomics and the intel- gent application of these tools to address biologically relevant questions. The RECOMB Workshop on Comparative Genomics (RECOMB-CG) is devoted to bringingtogetherscientistsworkingonallaspectsofcomparativegenomics, from the development of new computational approaches to genome sequence analysis andcomparison, to the genome-wideapplicationofcomputationaltools to study the evolutionary dynamics of prokaryotic and eukaryotic genomes. This volume contains the 19 papers presented at the 6th Annual RECOMB- CG workshop held during October 13-15 at the Ecole Normale Sup erieure, in Paris, France. The papers selected for presentation and published in these p- ceedings were selected from 48 submissions from scientists around the world. Each paper was reviewed by at least three members of the Program Committee in a stringent and thoughtful peer-review process."