Diverse mechanisms for pH sensing and cytoplasmic pH homeostasis enable most bacteria to tolerate or grow at external pH values that are outside the cytoplasmic pH range they must maintain for growth. The most extreme cases are exemplified by the extremophiles that inhabit environments with a pH of below 3 or above 11. Here, we describe how recent insights into the structure and function of key molecules and their regulators reveal novel strategies of bacterial pH homeostasis. These insights may help us to target certain pathogens more accurately and to harness the capacities of environmental bacteria more efficiently.