During the past decades, the exploration of new alkyne amination reactions has attracted increasing attention due to the high efficiency in heterocycle synthesis. In addition to the well-established alkyne amination reagents (such as nitrogen ylides and azides), isoxazoles and their derivatives have been proven to be efficient amination reagents, especially the N,O-bifunctional reagents of alkynes, in the transition metal-catalyzed transformation of alkynes through metal carbene intermediates. Isoxazole derivatives have been extensively applied to the rapid synthesis of a diverse range of structurally complex N-containing molecules, especially the valuable N-heterocycles in atom-economic manner. In this review, we summarize the latest trends and developments of isoxazole-enabled alkyne amination reactions and their applications in divergent heterocycle synthesis, including amination of ynamides, amination of ynol ethers, amination of thioynol ethers, amination of electron-deficient alkynes, amination of unpolarized alkynes and asymmetric amination of alkynes. Finally, we list the current challenges and opportunities for potential breakthroughs in this field.