The xCELLigence Real Time Cellular Analysis (RTCA) system from Roche Applied Sciences allows for the real-time assessment of cell morphology, growth and attachment in disease-relevant cells, under label-free conditions.Cells are seeded onto plates containing microelectrode biosensors, resulting in alteration of the electrical impedance observed when an electric field is applied to the system.The resulting impedance readout, expressed as a Cell Index value, allows for rapid and precise measurement of subtle changes in cellular morphology or attachment, as well as long term proliferation and cytotoxicity, in response to compound treatment:In contrast to traditional target or pathway specific assays, the impedance readout can potentially capture the net effects of all the biologically relevant signaling pathways that can impact a cellular phenotype.For many targets, this methodology allows for evaluation of endogenously expressed targets and pathways in a therapeutically relevant cellular context, and is thus a perfect fit for phenotypic approaches to drug discovery.Phenotypic assays have the potential to circumvent the high attrition rates observed in traditional target-based HTS campaigns, and in fact are historically the source of a large fraction of FDA approved "first in class" molecules (Swinney & Anthony, 2011).