Ehrlichia ruminantium is an obligate intracellular pathogenic bacterium that causes heartwater, a fatal disease of ruminants in tropical areas. Some human cases have also been reported. This globally important pathogen is primarily transmitted by ticks of the Amblyomma genus and threatens American mainland. E. ruminantium replicates within eukaryotic mammal or tick cell is a membrane-bound vacuole, where it undergoes a biphasic developmental growth cycle and differentiates from noninfectious replicative form into infectious elementary bodies. The ability of E. ruminantium to hijack host cellular processes and avoid innate immunity is a fundamental, but not yet fully understood, virulence trait of this stealth pathogen in the genomic era.