This book constitutes the refereed proceedings of the 5th RECOMB Comparative Genomics Satellite Workshop, RECOMB-CG 2007, held in San Diego, CA, USA, in September 2007. The 14 revised full papers presented address a broad variety of aspects and components of the field of comparative genomics, ranging from quantitative discoveries about genome structure to algorithms for comparative inference to theorems on the complexity of computational problems required for genome comparison.