Many bacterial pathogens replicate inside human cells by avoiding cell intrinsic innate immune pathways. This subversion of host cell signalling by intracellular pathogens more than often requires the transport of bacterial virulence effector proteins into the infected cell. Many effector proteins are enzymes that mediate the posttranslational modification of host proteins to block anti-microbial host responses. We recently identified effector proteases from Shigella, that target type I interferon signalling by inactivating key transcription factors involved in the interferon response. We also recently identified an effector protein from Legionella that drives degradation of a specific subset of mRNAs during infection of human macrophages. The activities of effector proteins can provide new insight into the inflammatory, cell death and cell intrinsic defense pathways that restrain pathogen replication and are important tools to understand the innate responses required for pathogen control.