Fused heterocycles constitute the largest diversity of heterocyclic compounds of chemical and biomedical significance. They widely exist in numerous natural products. They are also among the most frequently encountered scaffolds in numerous drugs and pharmaceutically relevant substances. This review highlights some remarkable achievements made in the synthesis and chemistry of pyridotriazolopyrimidines that have appeared in more than the last three decades. The latter heterocyclic ring systems have more than twenty five structures. Moreover, the biological importance of such ring systems is discussed.