Isothermal titration calorimetry (ITC) is a useful technique to study RNA-protein interactions as it provides the only method by which the thermodynamic parameters of free energy, enthalpy, and entropy can be directly determined. This chapter presents a general procedure for studying RNA-protein interactions using ITC and gives specific examples for monitoring the binding ofCaenorhabditis elegansGLD-1 STAR domain to TGE RNA and the binding ofAquifex aeolicusS6:S18 ribosomal protein heterodimer to an S15-ribosomal RNA complex.