The first protein structures were determined in the 1950s. In the decades that followed, development of new methods for sample preparation, crystallization, data collection, and structure analysis yielded tens of thousands of biomolecular structures. This short review highlights some of the major technical advances exemplified with selected structures. © 2013 The Authors. Published by Wiley Periodicals, Inc. Biopolymers 99: 817–824, 2013.