The main reasons why powder-diffraction data from proteins and protein complexes have such high potential are: (i) powders are easily prepared under a wide range of conditions and are not subject to the restricted circumstances required for growing suitable single crystals; (ii) protein powders are inherently `perfect' for diffraction; the individual crystallites are of the right size (about 1 µm) and are almost completely strain free; and (iii) data can be collected rapidly, making the observation of many dynamic processes straightforward. This chapter aims to guide current and future practitioners on how to undertake macromolecular powder-diffraction studies in a thorough, precise and accurate manner and with good understanding of the core principles. Following a general survey of examples, several case studies are used as detailed illustrations. Synchrotron beamline options are described, including their respective advantages and disadvantages. A wide range of software exists for powder-diffraction data processing and analyses, some of which has been adapted to large-unit-cell studies, and is briefly described; these software suites change more rapidly than hardware configurations and it is best to consult the relevant software package user manuals in such cases. Over a period of hardly more than ten years macromolecular powder diffraction has moved from an impossible dream to a reality, as exemplified by characterizing bulk pharmaceuticals, the molecular-replacement structure determination of the protein ponsin, the moving forward of the structure determination of a Trinidadian virus which will not yield sizeable single crystals, the combination of powder-diffraction X-ray data with techniques such as cryo-electron microscopy, and the combination of single-crystal data from micron-sized crystals with powder-diffraction data. Future developments move towards structure determination using isomorphous heavy-atom derivatives and anomalous dispersion. Prospects for the future include femtosecond X-ray laser time-resolved diffraction and electron-diffraction studies of nanocrystals.