Since 1994, approximately a thousand new publications have appeared in the literature, wherein a mention of 1,3,5-oxadiazines or 1,3,5-thiadiazines has been made. In addition to the ring systems mentioned in CHEC-II(1996), a number of new systems have appeared in the literature over the last decade. The presence of an imine functionality attached to the ring is a characteristic of reports in recent years. A number of fused ring systems have also been reported. The discovery of the potent nicotinoid insecticide, thiamethoxam, has prompted intensive research in the area of 1,3,5-oxadiazines. Tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives, due to their high lipid solubility and enzymatic rate of hydrolysis, have been utilized as prodrugs. A number of publications appear on the use of 1,3,5-oxadiazines as the fundamental building blocks for the synthesis of curcurbituril, its derivatives, and congeners. New syntheses involving ring expansions of the imidazole and thiazole rings have been reported. Preparative methods on solid supports as well as gas phase and electrochemical syntheses have also been published. The first report of a naturally occurring 1,3,5-oxadiazine system has been made. Sensitive analytical methods to detect very small concentrations of pesticides such as thiomethoxam have been developed. The crystallographic analyses of a vast number of 1,3,5-oxa- and thiadiazines have been reported. Physical methodology, theoretical aspects, synthesis, reactivity, and utility of 1,3,5-oxadiazines and 1,3,5-thiadiazines are reviewed in this chapter.