Genetically encoded probes for the optical imaging of excitable cell activity have been constructed by fusing fluorescent proteins to functional proteins that are involved in physiological signaling systems, such as those that control membrane potential, free calcium and cyclic nucleotide concentrations and pH. Using specific promoters and targeting signals, the probes are introduced into an intact organism and directed to specific tissue regions, cell types, and subcellular compartments, thereby extracting specific signals more efficiently and in a more relevant physiological context than before. Optical imaging using genetically encoded probes has enabled us to decipher spatio-temporal information coded in complex tissues.