Potassium (K+) channels are the most diverse class of ion channels, and are important for regulating neuronal excitability and signaling activity in a variety of ways. They are major determinants of membrane excitability, influencing the resting potential of membranes, wave forms and frequencies of action potentials, and thresholds of excitation. Voltage-gated K+ cannels exist not as independent units merely responding to changes in transmembrane potential but as macromolecular complexes able to integrate a plethora of cellular signals that fine tune channel activities. There are a wide variety of therapeutic agents that are targeted to non-K+ channels, but result in unintended block of K+ channels. This K+ channel block can result in potentially serious and sometimes even fatal side effects.