Publisher Summary This chapter introduces the chemistry of the 1,3,4-oxadiazoles. The 1,3,4-oxadiazoles have large number of applications in diverse areas—for example, in drug syntheses, scintillation materials, and the dyestuffs industry. Ring cleavage reactions of the 1,3,4-oxadiazoles have also excited great interest in various fields, because they lead to new aliphatic nitrogen-containing compounds and to other ring systems. The chapter explores the syntheses, the reactivity, the physical properties, and the uses of 1,3,4-oxadiazoles. The chapter presents the preparation of 1,3,4-oxadiazoles by ring closure of chains with a preformed 1,3,4-oxadiazole skeleton, syntheses from acid hydrazides by the introduction of a one-carbon fragment from other ring systems, other syntheses and condensed 1,3,4-oxadiazoles. The reactivity of the 1,3,4-oxadiazoles includes substitution reactions and structure of 1,3,4-oxadiazoles and reactions proceeding with ring cleavage. The 1,3,4-oxadiazole system has an electronic spectrum equivalent to that of benzene and the maxima of the oxadiazole derivatives are only slightly shifted hypsochromically compared with benzene. The chapter explains electronic and nuclear resonance spectra that have been increasingly drawn upon in the elucidation of the structures of 1,3,4-oxadiazole derivatives. The growing patent literature of recent years demonstrates that the 1,3,4-oxadiazoles are becoming of great practical significance.