An understanding of why certain Acinetobacter species are more successful in causing nosocomial infections, transmission and epidemic spread in healthcare institutions compared with other species is lacking. This talk will describe some of the genomic, phenotypic and virulence studies that we have used to identify differences between Acinetobacter species that help promote some to succeed and survive in niche environments. The talk will also describe the identification of an A. baumannii global virulence regulator that appears important in the regulation of key virulence attributes such as motility, biofilms and virulence toward mammals.