During infection, most pathogenic bacteria deliver proteins to the host cell cytoplasm to manipulate host behavior. In this issue of Cell Host & Microbe, Spanò and colleagues describe a system where a bacterium produces an exotoxin while inside the host cell. Only after this exotoxin is transported to the mammalian cell surface and secreted into the extracellular milieu can it intoxicate the infected cell or noninfected distant cells.