AbstractIsoxazolines are nitrogen‐ and oxygen‐containing five‐membered heterocyclic scaffolds with extensive biological activities. This framework can be readily obtained in good to excellent yields through 1,3‐dipolar cycloaddition between nitrones with alkynes or allenes, aryl/alkyl halides, alkynes, and oxaziridines under mild conditions. This scaffold has been an emerging area of interest for many researchers given their wide range of bioactivities. Herein we review synthetic strategies toward isoxazolines and the role these efforts have had in enhancing the biological activity of natural products and synthetic compounds such as antitubercular agents, COX‐1 inhibitors, COX‐2 inhibitors (e. g., valdecoxib), nicotinic receptor modulators, and MIF inhibitors. With a focus on efforts from 2010 onward, this review provides in‐depth coverage of the design and biological evaluation of isoxazoline systems and their impact on various pathologies.