Abstract: Cel-based or phenotypic drug discovery offers potential advantages, including the discovery of unexpected molecular mechanisms, identification of molecules with celular activity, and the possibility of drug repurposing to speed clinical translation. This lecture wi l provide an overview of different screening approaches and analysis methods using transcriptional, morphological, and fitness-based readouts of drug activity. Examples of discoveries wi l include novel mechanisms that would have been missed by traditional in vitro target-based screens.