Recent improvements in instrument hardware, experimental design and data processing have made it possible to use surface plasmon resonance (SPR) biosensor technology in the discovery and development of small-molecule drugs. The key features of SPR biosensors (i.e. real-time binding analysis and lack of labeling requirements) make this technology suitable for a wide range of applications. Current instruments have a throughput of approximately 100-400 assays per day, providing a complement to secondary screening. The ability to collect kinetic data on compounds binding to therapeutic targets yields new information for lead optimization. Small-molecule analysis and emerging applications in the areas of ADME (adsorption, distribution, metabolism and excretion) and proteomics have SPR biosensors poised to play a significant role in the pharmaceutical industry.