Diffraction-based techniques are fundamental tools for the characterization and understanding of materials of different nature, including those relevant for the cultural heritage. Both conservation science and archaeometry thus may extensively profit from the information provided by diffraction techniques. The aims of the investigations include the issues of diagnostics and conservation of art works, and analysis and interpretation of archaeological artifacts related to human past. The various methods and techniques of single-crystal and powder diffraction as applied to cultural heritage materials are briefly described with reference to specific examples, with focus on the extracted information in terms of (1) phase identification and quantification of crystalline compounds and complex polyphasic mixtures, (2) the texture and orientation of the crystalline phases, (3) the atomic and molecular structure of the phases involved, and (4) the physical microstructural state of the material in terms of crystallite size and accumulated strain. A few trends are evidenced in the present day development of diffraction instrumentation and techniques applied to cultural heritage materials, including the use of portable instrumentation, the access to large scale facilities, and the combined use of diffraction and imaging techniques.