Publisher Summary The aim of the chapter is to present a coherent survey of the chemistry of isothiazoles in the light of the numerous developments, which have taken place since the subject was last reviewed in 1965. The chapter begins with synthesis of mononuclear isothiazoles where it attempts to rationalize the numerous routes, now available to the isothiazole ring system. It has discussed about preparation of isothiazoles from bicyclic systems, preparation of isothiazoles involving oxidative formation of a nitrogen-sulfur bond, preparation of isothiazoles from olefins, preparation of isothiazoles from acetylenes, preparation of isothiazoles from 15-mercaptoacrylonitriles and related compounds, preparation of isothiazoles from 1,2-dithiolium salts, and preparation of isothiazoles from β-aminocrotonate and thiophosgene. The Physiochemical Properties of Isothiazoles are described in the chapter where ultraviolet spectra, infrared spectra, nuclear magnetic resonance spectra, and mass spectra are presented. The isothiazoles possess the typical properties of a heterocyclic aromatic system without the ring lability so characteristic of the analogous isoxazoles. The chemistry reflects the relative inertness of the 3-position, the susceptibility of the 4-position to electrophilic attack, and the susceptibility of the 5-position to nucleophilic attack. Electrophilic substitution reactions, metallation reactions, alkyl- and arylisothiazoles, aminoisothiazoles, halogenoisothiazoles, hydroxy- and alkoxyisothiazoles, isothiazolecarboxylic acids, amides, and nitriles, isothiazole aldehydes and ketones, isothiazole thiols, alkylthiols, and sulfides, and quaternary isothiazoles are covered in this section. The chapter has also discusses about reactions involving cleavage of the isothiazole ring, photochemical reactions of isothiazoles, and biologically active isothiazoles.