Potassium is an essential mineral nutrient present in all organisms as the monovalent cation K+. The coordination chemistry of ionic potassium governs its physiological interactions, underpinning electrical excitability in nerve and muscle as well as electrolyte balance, blood pressure, cell volume regulation and downstream metabolic processes. The common link between these functions is the establishment and maintenance of a membrane potential. To retain membrane excitability, intracellular and extracellular K+ concentrations must be maintained within stringent limits. A failure to adequately regulate K+ levels can have dire physiological consequences under the broad umbrellas of hypo- and hyper-kalaemia. In multicellular organisms, K+ homeostasis entails both short- and long-term measures. Homeostatic processes involve interplay between ion channels and co-transporters differentially expressed in specific cell types or tissues. In the human central nervous system, for example, K+ uptake and spatial buffering mechanisms enable reinstatement of the membrane potential following action potentials. Electroneutrality is maintained by a complex balancing act between electrolyte species. In prokaryotes, the ability to actively accumulate K+ and maintain a potential driving force across the periplasmic membrane is critical to cellular integrity, cell volume regulation, cellular morphology, cell division, pH sensing and possibly intercellular communication.