During last decade there has been significant progress in the development of analytical techniques for evaluation of receptor-ligand interaction. Surface plasmon resonance (SPR)-based optical biosensors are now being used extensively to define the kinetics of wide variety of macromolecular interactions and high- and low-affinity small molecule interactions. The experimental design data analysis methods are evolving along with widespread applications in ligand fishing, microbiology, virology, host-pathogen interaction, epitope mapping, and protein-, cell-, membrane-, nucleic acid-protein interactions. SPR-based biosensors have strong impact on basic and applied research significantly. This brief review describes the SPR technology and few of its applications in relation to receptor-ligand interaction that has brought significant change in the methodology, analysis, interpretation, and application of the SPR technology.