Technical Abstract: Renibacterium salmoninarum (Rs) is the causative agent of bacterial kidney disease and a significant threat to the healthy and sustainable production of salmonid fish worldwide. The pathogen is difficult to culture in vitro, genetic manipulation is challenging, and current therapies and preventative strategies are only marginally effective in preventing disease. The complete genome of R. salmoninarum ATCC 33209 was sequenced and shown to be a circular chromosome of 3,155,250 bp that is predicted to encode 3,507 open-reading frames (ORFs). There are a total of 80 copies of three different insertion sequence (IS) elements interspersed throughout the genome. Approximately 21% of the predicted ORFs have been inactivated via frameshifts, point mutations, insertion sequences and putative deletions. The Rs genome has extended regions of synteny to Arthrobacter sp. FB24 and A. aurescens TC1, but is approximately 1.9 Mb smaller than both Arthrobacter spp. genomes with a lower G+C content, suggesting significant genome reduction has occurred since divergence from the last common ancestor. A limited set of putative virulence factors appear to have been acquired via horizontal transmission after divergence of the species; these include capsular polysaccharides, heme sequestration molecules, and the major secreted cell surface antigen p57 (also known as major soluble antigen). Examination of the genome reveals a number of ORFs homologous to antibiotic resistance genes, including ß-lactamases, efflux proteins, macrolide glycosyltransferases, and ribosomal RNA methyltransferases. The genome sequence provides new insights into Rs evolution and may facilitate identification of chemotherapeutic targets and vaccine candidates for future utility in prevention and treatment of infections in cultured salmonids.