Many bacterial pathogens use specialised protein secretion systems to inject so-called “effector” proteins into eukaryotic host cells. In the last 10 years, it has emerged that bacterial effector proteins are typically enzymes that sometimes mediate highly novel post-translational modifications of eukaryotic proteins. Recent examples include arginine glycosylation, phosphoribosyl-linked ubiquitination and ADP-riboxanation. As such, bacterial effectors are unique tools to explore fundamental aspects of cell biology and biochemistry. In addition, the identification of the targets of effector activity in host cells provides valuable insight into host mechanisms of cell intrinsic immunity, since effector proteins have evolved to block these pathways. While it is well established that bacterial effectors target eukaryotic proteins using an arsenal of post-translational modifications, bacterial effectors that modify host RNA are less common. Excitingly, we recently discovered a Legionella effector protein that degrades host glycolytic mRNAs to inhibit host cell metabolism during infection, thereby introducing the possibility that effector proteins also target the host epitranscriptome.