The recent sequencing of the human genome has created comprehensive information of all potential drug targets. Based on current estimations for the total number of genes, around 400 poreforming ion channel genes can be expected corresponding to about 1.3% of the human genome. Since many ion channels are involved in diseases and the currently marketed drugs act only on a small fraction of these pore-forming membrane proteins, there is a big opportunity for innovative ion channel drug discovery. In fact, recent advances in the development of functional ion channel assays are currently enabling a more systematic exploitation of this important target class. In particular, fluorescence-based methods, automated electrophysiology, and ion flux assays are most important in this regard. This article will briefly describe these methods focusing on the nonradioactive Rb(+) efflux assay that I developed in the early 1990s since it has found widespread application in drug discovery and development and greatly displaced (86)Rb(+) assays for the analysis of K(+) and nonselective cation channels in the pharmaceutical industry.