Nuclear magnetic resonance (NMR) spectroscopy in solution has evolved into a powerful technique for structure determination of proteins and nucleic acids. More recently, a number of NMR-based approaches have been developed to monitor and characterize intermolecular interactions. These approaches offer unique advantages over other techniques and find their utility in both structural biology and drug discovery. We will report on basic principles and recent examples of the application of such NMR methodologies to characterize protein-protein interactions and for ligand binding studies and drug discovery.