Inward‐rectifier potassium (K_ir) channels comprise a superfamily of potassium (K⁺) channels with unique structural and functional properties. Expressed in virtually all types of cells they are responsible for setting the resting membrane potential, controlling the excitation threshold and secreting K⁺ ions. All K_ir channels present an inwardly rectifying current–voltage relation, meaning that at any given driving force the inward flow of K⁺ ions exceeds the outward flow for the opposite driving force. This inward‐rectification is due to a voltage‐dependent block of the channel pore by intracellular polyamines and magnesium. The present molecular–biophysical understanding of inward‐rectification and its physiological consequences is the topic of this review. In addition to polyamines, K_ir channels are gated by intracellular protons, G‐proteins, ATP and phospholipids depending on the respective K_ir subfamily as detailed in the following review articles.