Two-pore-domain K+ (K(2P)) channels are a diverse and highly regulated superfamily of channels that are thought to provide baseline regulation of membrane excitability. Of these, the TREK channels are expressed highly in the human CNS, and can be activated by temperature, membrane stretch and internal acidosis. In addition, TREK channels are sensitively activated by certain polyunsaturated fatty acids that have been shown to have neuroprotective activity and by volatile and gaseous general anaesthetics. New data derived from studies of knockout animals suggest that TREK-1 might have an important role in the general anaesthetic properties of volatile agents, such as halothane, and provide an explanation for the neuroprotective properties of polyunsaturated fatty acids.