Publisher Summary This chapter focuses on the chemistry of 1,2,4-oxadiazoles and the corresponding reduced derivatives. The chapter discusses the synthesis of 1,2,4-oxadiazoles. Two widely used general methods of synthesizing 1,2,4-oxadiazoles embrace 95% of the practical preparations of these compounds: The conversion of amidoximes by means of carboxylic acid derivatives to the cyclic structure and the cycloaddition of nitrile oxides to nitriles (II). Synthesis of 1,2,4-oxadiazoles from O-acylamidoximes, N-acyliminoethers, and C-nitroso derivatives is discussed. The most widely used method of synthesizing oxadiazoles is the cyclization of O-acylamidoximes. Aldoximes may be used as starting compounds for amidoximes. The amidoximes may then be converted into O-acyl derivatives, which is an intermediate in the pathway to oxadiazoles. Furthermore, the chapter describes the physical properties, such as electron density and molecular geometry, thermodynamic functions, and dipole moments. Chemical properties, such as thermal stability, photochemical effects, and functional group chemistry of 1,2,4-oxadiazoles is discussed. Finally, the chapter illustrates the use of 1,2,4-oxadiazoles in chemotherapy and agriculture.