Secretion systems play a central role in infectious diseases by enabling pathogenic bacteria to deliver virulence factors into target cells. The type VI secretion system (T6SS) mediates bacterial antagonism in various environments including eukaryotic niches, such as the gut. This molecular machine injects lethal toxins directly in target bacterial cells. It provides an advantage to pathogens encountering the commensal flora of the host and indirectly contributes to colonization and persistence. Yet, the T6SS is not employed for the sole purpose of bacterial killing and several T6SS effectors are dedicated to the subversion of eukaryotic cells. As described for type III and type IV secretion systems, these effectors impede host cell functions and promote immune evasion, thereby enabling successful infection.