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Protein secretion is important for many biotic and abiotic interactions. The evolution of protein secretion systems of bacteria, and related nanomachines, occurred by the co-option of machineries for motility, conjugation, injection, or adhesion. Some of these secretion systems emerged many times, whereas others are unique. In most cases, their evolution occurred by successive rounds of gene accretion, deletion, and horizontal transfer, resulting in machines that can be very different from the original ones. The frequency with which such co-option processes occurred seems to depend on the complexity of the systems, their differences to the ancestral machines, the availability of genetic material to tinker with, and possibly on the mechanisms of effector recognition. Understanding the evolution of secretion systems illuminates their functional diversification and could drive the discovery of novel systems.