Large-conductance Ca(2+)-activated K(+) channels (BK channels) constitute an key physiological link between cellular Ca(2+) signaling and electrical signaling at the plasma membrane. Thus these channels are critical to the control of action potential firing and neurotransmitter release in several types of neurons, as well as the dynamic control of smooth muscle tone in resistance arteries, airway, and bladder. Recent advances in our understanding of K(+) channel structure and function have led to new insight toward the molecular mechanisms of opening and closing (gating) of these channels. Here we will focus on mechanisms of BK channel gating by Ca(2+), transmembrane voltage, and auxiliary subunit proteins.