Our Protein Interaction Core is part of an existing Core facility within the University of Utah’s Health Sciences Core facilities. The Protein Interaction Core facility was established in 1996 to provide internal and external academic users access to state-of-the-art, label-free, real-time interaction technologies. Over the past 10 years, this facility has contributed to more than 100 research projects that encompass a wide array of biological areas. The Protein Interaction Core is centrally located within the School of Medicine (Rm 4A416) on the Health Sciences campus of the University of Utah. The laboratory’s 1600 square feet of space was entirely renovated in 1997 and was specifically designed to accommodate the Core facility’s equipment and personnel. Currently, the facility maintains 7 surface plasmon resonance-based optical biosensors: 3 Biacore 2000s, 1 Biacore 3000, 1 Biacore S51, 1 Biacore Flexchip, and 1 BioRad ProteOn XPR36. The Biacore 2000/3000 platforms are ideal for measuring protein-protein interactions, while the Biacore S51 is designed for small-molecule interaction analysis. The Flexchip and ProteOn instruments are array-based imaging systems that allow us to scale up the number of binding partners immobilized onto the sensor surface. Using these technologies, we can examine >100 interactions at one time. The Core has worked closely with both Biacore and BioRad on the development of this new hardware, as well as data analysis software. Together, these state-of-the-art instruments allow us to measure the interactions of biomolecules such as proteins, oligonucleotides, and lipids in high-resolution, as well as high-throughput, formats.