Microorganisms that have a pH optimum for growth of less than pH 3 are termed "acidophiles". To grow at low pH, acidophiles must maintain a pH gradient of several pH units across the cellular membrane while producing ATP by the influx of protons through the F(0)F(1) ATPase. Recent advances in the biochemical analysis of acidophiles coupled to sequencing of several genomes have shed new insights into acidophile pH homeostatic mechanisms. Acidophiles seem to share distinctive structural and functional characteristics including a reversed membrane potential, highly impermeable cell membranes and a predominance of secondary transporters. Also, once protons enter the cytoplasm, methods are required to alleviate effects of a lowered internal pH. This review highlights recent insights regarding how acidophiles are able to survive and grow in these extreme conditions.