The 5‐alkoxyoxazole ring system has proved to be a useful and versatile building block that is involved in a variety of chemical transformations (e.g., hetero‐Diels–Alder reactions, formal 1,3‐dipolar cycloadditions, photochemical [2+2] cycloadditions, Claisen rearrangements, and ring‐opening processes). 5‐Alkoxyoxazoles have provided synthetic access to heteroaromatic scaffolds such as pyridines, furans, oxadiazolines, pyrrolidines, and significant linear chemical patterns, including amino acid derivatives. This review focuses on the broad range of reactivity of 5‐alkoxyoxazoles and their subsequent applications to the syntheses of naturally occurring compounds and biologically active molecules.