Surface plasmon resonance (SPR) is a novel biophysical detection method. In combination with sophisticated surface chemistries and sensing instrumentations, SPR biosensors are approved as tools for molecular interaction studies. SPR plays also a role in interaction proteomics. Once being detected in urine, SPR helps to unravel the functions of new proteins. Due to its outstanding analytical characteristics, SPR also moves more and more into the realm of quantitative analyses in the clinical laboratory. Complex urine determinations of proteins and/or metabolites will bring the SPR biosensor both to the core lab and to point-of-care-testing.This review delineates first the optical phenomena of SPR near to the gold surface, and also the main features of bioconjugation chemistry on a solid-state surface. Then the kinetic calculation of molecular interaction analysis using SPR is introduced. In order to portray the capability of the method, new applications in urine proteomics and proteinuria diagnostics are finally described in detail.