Development of X-ray diffractometry at the turn of the 20th and 21st centuries is presented. The review covers instrumentation development for structural studies based on the usage of both standard continuously radiating X-ray generators and state-of-the-art sources of ultrashort and ultra-bright X-ray pulses. The latter technique enables investigation of the structural dynamics of condensed matter in a 4D space-time continuum with a resolution of up to a tenth of femtosecond. New engineering approaches to enhancing sensitivity, accuracy, and efficiency of X-ray diffraction experiments are discussed including new and promising X-rays sources, reflective collimating and focusing X-ray optics, fast low-noise and radiation-resistant position-sensitive X-ray detectors, as well as a new generation of X-ray diffractometers developed based on these elements. Presentation is focused on modern engineering solutions that enable academic and applied-research laboratories to perform on-site the X-ray diffraction studies that earlier were only feasible using synchrotron radiation sources at international resource sharing centers.