Since the first NMR spectrum of a protein was published over 50 years ago, remarkable technical improvements have led to NMR being recognized as a uniquely powerful tool that can give a wide variety of useful information about macromolecules and their interactions. This article gives an overview of NMR studies of proteins. It presents a personal historical perspective, briefly reviews the current status of the field and reflects on possible future directions. Two specific examples, related to multi-domain complexes and membrane-spanning adhesion receptors, are described to illustrate recent applications. Emphasis is placed on how general advances in molecular biology and technology are changing the nature and focus of NMR studies.