Kv7.x channels are a family of six transmembrane domain, single pore-loop, voltage-gated K(+) channels. Five members of the family have been identified to date, including the cardiac channel Kv7.1 (formerly known as KvLQT1) and four neuronal Kv7.x channels, Kv7.2-5. Heteromeric channels containing Kv7.3 and either Kv7.2 or Kv7.5 are thought to underlie the neuronal M-current, a non-inactivating, slowly deactivating, sub-threshold current that has long been known to exert a powerful stabilizing influence on neuronal excitability. Modulators of these channels have the potential to influence neuronal activity in various tissues and are of much interest as therapeutic drug targets for the treatment of a variety of clinical disorders, such as epilepsy and pain. The purpose of the present article is to review the molecular, functional and behavioral evidence validating Kv7.x as drug targets for the treatment of pain. In addition, an update on pre-clinical Kv7 drug discovery efforts will be presented, along with a summary of on-going clinical trials with Kv7 channel activators.