Biosensors based on specific interaction of the analyte of interest (ligand) with a biochemical agent (receptor) which specifically and tightly binds the analyte are being developed by many groups, agencies, and institutions using a variety of detection technologies. We are studying fluorescent methods using evanescent wave excitation on the surface of planar and cylindrical (fiber optic) optical waveguides. A relatively low ligand-receptor binding constant results in reversibility but low sensitivity. Most biological receptors bind very strongly and specifically--almost irreversibly--which provides an "irreversible" means of detection. Means to regulate ligand-receptor binding constants are discussed in order to provide semi-reversible, sensitive, specific sensors, rather than "one-shot" detectors or dosimeters.