Comparative genomics of Arabidopsis relatives has great potential to improve our understanding of molecular function and evolutionary processes. Recent studies of phylogenetic relationships within Brassicaceae and the publication of a new tribal classification scheme provide an important framework for comparative genomics research. Comparative linkage mapping and chromosome painting in the close relatives of Arabidopsis have inferred an ancestral karyotype of these species. In addition, comparative mapping to Brassica has identified genomic blocks that have been maintained since the divergence of the Arabidopsis and Brassica lineages. Several analyses of conserved non-coding regions have identified putative cis-regulatory sequences, and have highlighted the need for comparative sequencing at greater evolutionary distances. The development of new model species with novel physiological and ecological traits allows analysis of phenotypes that are not available in A. thaliana. Looking towards the future, we suggest a prioritized research agenda for comparative genomics in the Brassicaceae.