There are three main classes of proton-ATPases named P-, V- and F-ATPases. Their function is to synthesize ATP from a universal high-energy intermediate (protonmotive force), or to generate the intermediate by hydrolysing ATP. Every cell contains at least one kind of these enzymes and the protonmotive force is used for numerous secondary reactions, including uptake and storage of neurotransmitters in synaptic vesicles. The ubiquitous distribution of proton-ATPases and their central role in energy conversion makes them indispensable components of cell metabolism. One of the functions of V-ATPases is to acidify the interior of organelles inside the cell. As Nathan Nelson discusses here, this property is being used for designing and targeting of drugs.