Many important crystalline solids cannot be prepared as single crystals of suitable size and quality for structural characterization by conventional single-crystal X-ray diffraction techniques and can instead be prepared only as microcrystalline powders. However, recent advances in techniques for determining crystal structures directly from powder X-ray diffraction data have created a unique opportunity for establishing structural properties of such materials. This chapter surveys the applications of powder X-ray diffraction across various aspects of structural and materials chemistry, focusing mainly on the opportunities that have emerged in recent years for carrying out complete crystal structure determination from powder X-ray diffraction data and giving particular emphasis to the case of molecular crystal structures. The current scope and future potential of powder X-ray diffraction as a strategy for crystal structure determination are discussed, and examples of applications across several disciplines of materials chemistry are presented.