The ATP synthases, also known as F-ATPases or F1Fo-ATPases, are multisubunit enzyme complexes found in energy transducing membranes in eubacteria, chloroplasts and mitochondria. They make ATP from ADP and phosphate under aerobic conditions using a proton-motive force, Δp, generated by respiration or photosynthesis, as a source of energy. The ATP synthases from these diverse sources have many common conserved structural features and mechanistic similarities, and all the enzymes operate by a rotary mechanism, where a rotor driven by the transmembrane proton motive force, transmits energy mechanically into the catalytic sites to drive the binding of substrates, and the formation and release of ATP. However, as enzymes from a wider range of species become investigated, significant differences are being uncovered, most notably in the energy cost of making each ATP molecule, and in the ways that the enzymes from various sources are regulated. Differences between the structures and regulatory mechanisms of the human enzyme, and the ATP synthases in bacterial and fungal pathogens, once understood in molecular detail, have the potential to be exploited systematically in the development of new drugs to combat antibiotic resistance in these microbes.