Ion channels represent a class of membrane spanning protein pores that mediate the flux of ions in a variety of cell types. To date, >400 ion channels have been cloned and characterized, and some of these channels have emerged as attractive drug targets. Several existing medications elicit their therapeutic effect through the modulation of ion channels, underscoring the importance of ion channels as a target class for modern drug discovery. To meet the increasing demand for high-throughput screening of ion channels, assay technologies have evolved rapidly over the past 5-10 years. In this article, the authors review the technologies that are currently used for the screening of ion channels. The technologies discussed are binding assays, ion flux assays, fluorescence-based assays, and automated patch-clamp instrumentation.