Abstract: N-sulfonyl triazole is an intermediate in organic synthesis and has been proven to be an excellent nitrogen source for the construction of many heterocycles. Due to its more favorable pharmacokinetic properties, tetrazole has also been proven to be a suitable bioisostere derived from a carboxylic acid and cisamide units. This chapter summarizes the new and innovative synthetic strategies that have been developed for the synthesis and ring-opening of N-sulfonyl triazoles and tetrazoles. This chapter covers the chemistry of N-sulfonyl triazole and tetrazole and their applications in medicine and pharmaceuticals. Initially, we discussed various synthetic methods of N-sulfonyl-1,2,3-triazoles, and then how reactive N-sulfonyltriazole is sufficient to open the ring and form acyclic amine derivatives (β-phenethylamine, o-diamine, allylamine, enamine, and Ketimine) or other cyclic N-sulfonylamines. This chapter also introduces the synthesis and use of N-sulfonyl-1,2,3,4-tetrazole. We focused on the synthetic development for the production of N-sulfonyl triazole and tetrazole and their reaction types.