Ralstonia solanacearum is a major phytopathogen that attacks many crops and other plants over a broad geographical range. The extensive genetic diversity of strains responsible for the various bacterial wilt diseases has in recent years led to the concept of an R. solanacearum species complex. Genome sequencing of more than 10 strains representative of the main phylogenetic groups has broadened our knowledge of the evolution and speciation of this pathogen and led to the identification of novel virulence-associated functions. Comparative genomic analyses are now opening the way for refined functional studies. The many molecular determinants involved in pathogenicity and host-range specificity are described, and we also summarize current understanding of their roles in pathogenesis and how their expression is tightly controlled by an intricate virulence regulatory network.