Several pathogenic bacteria secrete toxins to inhibit the immune system of the infected organism. Frequently, they catalyze a covalent modification of specific proteins. Thereby, they block production and/or secretion of antibodies or cytokines. Moreover, they disable migration of macrophages and disturb the barrier function of epithelia. In most cases, these toxins are extremely effective enzymes with high specificity towards their cellular substrates, which are often central signaling molecules. Moreover, they encompass the capacity to enter mammalian cells and to modify their substrates in the cytosol. A few molecules, at least of some toxins, are sufficient to change the cellular morphology and function of a cell or even kill a cell. Since many of those toxins are well studied concerning molecular mechanisms, cellular receptors, uptake routes, and structures, they are now widely used to analyze or to influence specific signaling pathways of mammalian cells. Here, we review the development of immunotoxins and targeted toxins for the treatment of a disease that is still hard to treat: cancer.