Proteins and RNA undergo intricate motions as they carry out functions in biological systems. These motions frequently entail large-scale conformational changes that induce changes in the surface structure, or shape, of a molecule. This review describes the experimental characterization of large-scale shape changes in proteins and macromolecular complexes and the effects of such changes on macromolecular behavior. We describe several important results that have been obtained by using small-angle scattering, which is emerging as a powerful technique for determining macromolecular shapes and elucidating the quaternary structure of macromolecular assemblies.