SPR (Surface Plasmon Resonance) biosensor instruments are more and more equipped to sensitively measure the binding characteristics of small molecules to their target. Via SPR biosensor measurements, not only the affinity of compounds but also other features such as the kinetics and thermodynamics aspects of binding can be determined. Furthermore, SPR is able to determine nonideal behavior of the fragment, such as aggregation and poor solubility binding. The use of SPR biosensors in various phases of the drug discovery process is evaluated. © 2010 Elsevier Ltd. All rights reserved.