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For every movement, heartbeat and thought, ion channels need to open and close. It is therefore not surprising that their malfunctioning leads to serious diseases. Currently, only approximately 10% of drugs, with a market value in excess of US$10 billion, act on ion channels. The systematic exploitation of this target class has started, enabled by novel assay technologies and fundamental advances of the structural and mechanistic understanding of channel function. The latter, which was rewarded with the Nobel Prize in 2003, has opened up an avenue for rational drug design. In this review we provide an overview of the current repertoire of screening technologies that has evolved to drive ion channel-targeted drug discovery towards new medicines of the future.