Green chemistry is a rapidly developing field providing a proactive avenue for the sustainable development of future science and technology. Green chemistry can be applied to the design of highly efficient, environmentally benign synthetic protocols to deliver life-saving medicines, and to accelerate lead optimization processes in drug discovery, while minimizing environmental impact. It also offers enhanced chemical process economics, concomitant with a reduced environmental burden. This review summarizes relatively environmentally benign protocols for the synthesis of pharmaceutically active heterocycles that highlight the advantages of using green chemistry, for example, by proceeding under microwave irradiation or in aqueous reaction media.