<p>Fifty years ago, Erwin Neher and Bert Sakmann published a <i>Nature</i> paper on their recording of discrete, step-like currents of a few picoamps passing through individual acetylcholine receptor channels of frog muscle fibers. This observation, the first on native channels, immediately ended the decade-long dispute about the presence of ion channels on cell membranes by convincing even the most reluctant scientists that this was indeed the case. More importantly, however, the ability to record single-channel currents revolutionized the study of ion channels because it enabled scientists to observe their behavior individually in real time. We could observe them change conformation, jumping from the closed state to the open state and back again. This level of detail provided an unprecedented understanding of the gating mechanisms, conductance, and kinetic properties of channels. This retrospective illustrates the scientific context in which all of this occurred as well as its immediate and current impact on the investigation of ion channels.</p> Graphical Abstract <p></p>