The evolution of protein secretion systems of Bacteria, and related nanomachines, remains enigmatic. Secretion is important for biotic and abiotic interactions, and secretion systems evolved by co-option of machinery for motility, conjugation, injection, or adhesion. Some secretion systems emerged many times, whereas others are unique. 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 of co-option depends 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 18 diversification and could drive the discovery of novel systems.