The pharmaceutical industry is presently suffering difficult times due to low productivity of new molecular entities.As a major source of drug leads,high-throughput screening(HTS)has been often criticized for its‘dead end’lead compounds.However,the fruitful achievements resulting from HTS technology indicate that it remains a feasible way for drug innovation.Because of increasing considerations of earlier stage ADMET(absorption,distribution,metabolism,excretion and toxicity)in drug development,cell-based HTS is highly recommended in modern drug discovery for its ability to detect more biologically relevant characteristics of compounds in living systems.This review provides a systematic and practical description of vital points for conducting high quality cell-based HTS,from assay development to optimization,compound management,data analyses,hit validation as well as lead identification.Potential problems and solutions are also covered.