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The vascular endothelium is the main target of a limited number of infectious agents; Rickettsia, Ehrlichia ruminantium, and Orientia tsutsugamushi are among them. These arthropod-transmitted obligately-intracellular bacteria cause serious systemic diseases that are not infrequently lethal. In this review, we discuss the bacterial biology, vector biology, and clinical aspects of these conditions with particular emphasis on the interactions of these bacteria with the vascular endothelium and how it responds to intracellular infection. The study of these bacteria in relevant in vivo models is likely to offer new insights into the physiology of the endothelium that have not been revealed by other models.