Single crystal and powder X-ray diffraction techniques helped define the actinide series during its genesis in the early twentieth century, and these are still helping forge new understanding in all actinides and especially the late actinides. The structural information provided by these techniques, including the three-dimensional structures of molecules and associated bond distances and angles, have laid the foundation for understanding chemical reactivity and properties in actinide materials. This article will give a brief overview of X-ray diffraction and the types of information this technique provides. The early history of actinide crystallography and the role it played in the development of the actinide series will be addressed. The common actinide isotopes used for crystallography will be described in terms of availability and hazards. An overview of important X-ray structures (Th–Cf) that helped advance actinide science, including the discovery of new valence states, chemical bonds, periodic trends, covalency, and other important phenomena, will be given. The article will close with potential pitfalls and corresponding solutions relevant to practicing actinide crystallography, addressing absorption, heavy atoms and pseudosymmetry, hydrogen atom location and refinement, and safe containment of radioisotopes.