A knowledge of the three-dimensional structure of a protein is essential to understand how a protein performs its functions. It is also a prime requirement for the rational design of novel sequences with specific structural, chemical or catalytic properties. Until recently, such information could only be obtained from X-ray diffraction studies on protein crystals. In the past few years, however, nuclear magnetic resonance (NMR) spectroscopy in solution has rapidly become established as an effective alternative method. This review briefly examines the two techniques and their relevance to protein engineering and design.