A critical component of the drug discovery and development process is the identification of novel pharmacophores. Such discovery efforts are, in general, facilitated by rapid and high-throughput cell-based assays of receptor/ion channel-mediated signaling processes to screen diverse chemical libraries of compounds possessing activator or inhibitor activities at the desired target. The availability of the Fluorometric Image Plate Reader (FLIPR) has made rapid assays of cellular signaling processes feasible by simultaneous kinetics measurement of cell-based fluorescence changes in a 96- or 384-well format. This unit describes the application of the FLIPR in cell-based kinetic assays for measuring membrane potential changes and intracellular calcium dynamics.