Recent discoveries of basal extracellular Rickettsiales have illuminated divergent evolutionary paths to host dependency in later-evolving lineages. Family Rickettsiaceae, primarily comprised of numerous protist- and invertebrate-associated species, also includes human pathogens from two genera, Orientia and Rickettsia. Once considered sister taxa, these bacteria form distinct lineages with newly appreciated lifestyles and morphological traits. Contrasting other rickettsial human pathogens in Family Anaplasmataceae, Orientia and Rickettsia species do not reside in host-derived vacuoles and lack glycolytic potential. With only a few described mechanisms, strategies for commandeering host glycolysis to support cytosolic growth remain to be discovered. While regulatory systems for this unique mode of intracellular parasitism are unclear, conjugative transposons unique to Orientia and Rickettsia species provide insights that are critical for determining how these obligate intracellular pathogens overtake eukaryotic cytosol.