Legionella pneumophila is an opportunistic bacterial pathogen that uses the Dot–Icm type IV secretion system (T4SS) to translocate effector proteins into host cells, which promote survival and replication of the pathogen. Buchrieser and colleagues analysed 80 Legionella strains belonging to 58 Legionella species and subspecies and report that the pan-genus pool of putative T4SS effectors comprises >18,000 proteins. In addition, the authors identified >200 eukaryotic-like proteins and 137 eukaryotic domains in the genomes of Legionella spp., including Rho-GTPase and Rab-GTPase domains, which were shown to be T4SS-secreted. Moreover, the repertoire of these proteins varied in different species, and the data suggest that these genes were mostly acquired through independent gene-gain events. The acquired genes might modulate specific eukaryotic host functions to promote intracellular survival and replication and may have led to the emergence of human Legionella pathogens.