This Review covers the synthesis and performance of the most promising 1,2,5-oxadiazole-based high-energy density materials (HEDMs). These materials comprise a 1,2,5-oxadiazole subunit as a key structural motif linked to various acyclic explosophoric groups or to nitrogen-rich and nitrogen-oxygen azoles: 1,2,4triazole, tetrazole, 1,2,4-and 1,3,4-oxadiazoles. Energetic alliances of two and more 1,2,5-oxadiazole rings linked directly or through heteroatom spacers are also presented. Particular attention is devoted to the installation of different explosophores: nitro, nitramino, azo, azoxy, dinitromethyl, trinitroethyl moieties and their combination. Promising environmentally benign energetic materials with high detonation velocity and pressure, and outstanding insensitivity are summarized. Overall, the presented materials may be considered as next-generation high-performance energetic materials that are superior to commonly used traditional explosives (TNT, PETN, RDX, HMX).