For a quarter of a century X-ray diffraction in single crystals was unique in its ability to solve three-dimensional structures of proteins and nucleic acids at atomic resolution. The situation changed in 1984 with the completion of a protein structure determination by nuclear magnetic resonance (NMR) spectroscopy in solution, and today NMR is a second widely used method for biomacromolecular structure determination. This review describes the method of NMR structure determination of biological macromolecules, and attempts to place NMR structure determination in perspective with X-ray crystallography. NMR is most powerful for studies of relatively small systems with molecular weights up to about 30000, but these structures can be obtained in near-physiological milieus. The two techniques have widely different time scales which afford different insights into internal molecular mobility as well as different views of protein or nucleic acid molecular surfaces and hydration. Generally, in addition to information on the average three-dimensional structure, NMR provides information on a wide array of short-lived transient conformational states. Combining information from the two methods can yield a more detailed insight into the structural basis of protein and nucleic acid functions, and thus provide a more reliable platform for rational drug design and the engineering of novel protein functions.