The study of matter at extreme conditions represents a forefront area of research activity across the sciences, including physics, chemistry, materials science, and even biology. Advancing the frontier of extreme conditions science requires powerful micro-sampling probes to access minute samples through the vessel walls and to separate weak sample signals from the background signals arising from the much more massive surrounding vessel materials. A plethora of x-ray diffraction (XRD), x-ray spectroscopy, and x-ray imaging techniques has been developed and integrated with high pressure and high/low temperature capabilities at HPCAT. High-pressure x-ray diffraction, using energy or angular dispersive modes, provides comprehensive crystallographic, electron density topology, bonding, grain boundary, elastic, and deformation information from single-crystal, polycrystalline, nanocrystalline, and noncrystalline substances.