The advent of the patch-clamp technique 25 years ago revolutionized the study of ion channels. This method also made it possible to measure the kinetic behavior of single protein molecules. The low-noise recordings of ionic currents through single channels, coupled with other cutting-edge technologies, have revealed a rich complexity of functional states that are not readily explained by simple allosteric protein models such as the popular concerted model and the sequential model. Although these models can each account for elements of ion channel function, we propose that variations or extensions of the lesser-known general allosteric model provide a more promising framework for explaining the intricate behaviors of ion channels.