Background or leak K+-selective channels, as defined by a lack of time and voltage dependency, play an essential role in setting the resting membrane potential and input resistance in excitable cells. Two-pore domain K+ (K2P) channels have been shown to conduct several leak K+ currents and they have been progressively identified over the last few years. Members of this KCNK family present structural features that suggest a dimeric arrangement, with each subunit comprising four transmembrane segments and two pore-forming K+-selective pores. The channels formed by members of this family are distinct from voltage-dependent or inwardly rectifying K+ channels in as much as most are constitutively active at resting membrane potentials and they generate currents that rectify only very weakly. K2P channels provide a wide variety of important functions, including the sensing of oxygen and pH, the setting of resting membrane potentials, the sensing of changes in [K+], the responses to agonists, and mechanosensitivity. These channels are also candidates for the action of volatile anaesthetics and of the alkalosis- and hypocarbia- dependent vasodilatory responses. Moreover, KCNQ channels appear to be promising candidates for the role in mediating the depolarizing action of hypoxia in pulmonary circulation and thus the hypoxic pulmonary vasoconstriction. Finally, K2P may also have a critical role in mediating the vasoactive response of G protein-coupled pathways in resistance arteries which can offer promising therapeutic solutions to target diseases of the circulation.