The concept of click chemistry represented by the formation of the 1,2,3-triazole core has found wide application in drug discovery, particularly in the early discovery phases and the lead optimization process. 1,2,3-Triazoles ha ve attracted considerable attention in recent years because of their wide range of biological activities against various viruses, malignant cells, microorganisms and their inhibitory activities against several enzymes. This review emphasizes the recent advances on diverse and potent biological profiles of 1,2,3-triazolo-nucleosides, along with emerging application of click chemistry in their synthesis, and their perspective in the development of new bioactive chemical entities in the future. The work is primarily addressed to antiviral, antimicrobial and anticancer potency of this important structural motifs in which the 1,2,3-triazole ring acts as a nucleobase surrogate or is linked to a nucleobase or a sugar/sugar mimic moiety.