Heterocyclic compounds are ubiquitous in biologically active compounds, including many drugs. Benzothiadiazine is a class of sulphur and nitrogen-containing heterocyclic compounds comprised of a benzene ring fused with thiadiazine. Benzothiadiazine rings appear in many marketed drugs, such as bendroflumethiazide, chlorothiazide, cyclothiazide, hydrochlorothiazide, and diazoxide, which are popularly known for their diuretic activity. The ring has diverse pharmacological activity, including anti-cancer, antifungal, antimicrobial, anthelmintic, hypolipidaemic, and antidiabetic activity. This chapter focuses on the chemistry, synthetic methods, and bioactivity of different benzothiadiazine. Furthermore, the updates on patents and clinical trials have also been summarized in the present chapter.