In recent years, optical evanescent wave biosensors have been used to characterize protein-protein interactions, including determination of equilibrium binding constants and bimolecular rate constants. This surface binding technique can provide information about chemical on-rate constants, the lifetimes of complexes formed, and the time course of the signal. This unit provides a thorough, well-illustrated discussion of the principles of optical biosensors, experimental design, ligand immobilization, experimental data analysis, and common obstacles and possible solutions.