Benzothiazole is a bicyclic heterocyclic compound that contains benzene fused with 1, 3-thiazole ring. Several researches established the potential of benzothiazoles as important moiety in various adverse pharmacological conditions. Benzothiazole and its derivatives have been in use and marketed as anti-microbial, anti-inflammatory, anti-diabetic, anti-oxidant, anti-convulsant, anti-tumor, etc. The variations in pharmacological potentials of the benzothiazole and its derivatives have been in rational with their chemical structure. Nowadays, hybridization of two or more pharmacophore to synthesize a single molecule with potent pharmacological action is used. This helps to synergize pharmacological properties, make interaction possible with many targets, or minimize the adverse effects associated with them. Several synthetic approaches have been reported for benzothiazole and its derivatives. In this present review, we focused on recently adopted synthetic approaches for the synthesis of the benzothiazole nucleus and its derivatives. The structure-activity relationship in relation with different pharmacological activities has also been highlighted to provide a good understanding to the researchers for future research on benzothiazoles.