Privileged structures can bind to a diverse range of targets with high affinities, thus benefiting the discovery of novel bioactive agents. 8-Hydroxyquinoline derivatives represent an important type of “privileged structure”, possessing a rich diversity of biological properties. Numerous encouraging investigations have demonstrated that this privileged structure should be further exploited for therapeutic applications in the future. In view of its predominance, and on the basis of our research interest in this scaffold, an updated and detailed account of the pharmacological properties of 8-hydroxyquinoline derivatives, as well as recent insights from structural biology, are described. Finally, some outlooks on current issues and future directions in this field of research are also provided.