During the past five years, several members of the KCNQ potassium channel gene family have been identified with a high degree of CNS specificity. Within the KCNQ family, the combination of the KCNQ2 / KCNQ3 proteins, and the KCNQ5 / KCNQ3 arrangement has been identified as the molecular correlates of the different M-currents. Several lines of evidence are emerging demonstrating the importance of these channels in regulating neuronal excitability; for example, determination of the excitability threshold, firing properties, and responsiveness of neurons to synaptic inputs. Recent studies have shown that KCNQ openers have potential for the treatment of several CNS disorders characterized by neuronal hyperexcitability, such as migraine, epilepsy and neuropathic pain. This article reviews the recent developments of KCNQ potassium channel openers.