We have seen a surge of research in development of fast and reliable HTS methods for ion channel targets. This is driven by the fact that hundreds of ion channel genes from the human genome project and their functional association with human diseases. Some of the channels have been proved to be important in the drug discovery process such as HERG and various calcium channels. Traditional potassium channel functional study has relied on Patch-Clamp electrophysiology and Rb86 efflux assay. However, those methods were not easily deployed for drug screening because of the concern for cost and speed. Pharmaceutical companies have relied on dye based ion channel readers such as FLIPR and VIPR for many years and the results are controversial. This talk will focus on the development of non-radioactive Rb+ efflux assay using ICR8000, a system designed for medium throughput functional HERG channel screening. The development of HTS ICR12000 will also be discussed.