Voltage-sensitive ion channels are macromolecules embedded in the membranes of nerve and muscle fibers of animals. Because of their physiological functions, biochemical structures and electrical switching properties, they are at an intersection of biology, chemistry and physics. Despite decades of intensive research under the traditional approach of gated structural pores, the relation between the structure of these molecules and their function remains enigmatic. This book critically examines physically oriented approaches not covered in other ion-channel books. It looks at optical and thermal as well as electrical data, and at studies in the frequency domain as well as in the time domain. Rather than presenting the reader with only an option of mechanistic models at an inappropriate pseudo-macroscopic scale, it emphasizes concepts established in organic chemistry and condensed state physics. The book s approach to the understanding of these unique structures breaks with the unproven view of ion channels as structurally gated pores. Rather, it proposes gateless gating, in which the onset and cessation of avalanches of ions crossing the membrane is explained as a cooperative phenomenon in a system poised far from equilibrium. These events, called channel opening and closing, are initiated by an electrical depolarization, a mechanical stimulus or even a thermal fluctuation.