 This review presents a comprehensive overview on selected synthetic roots towards commercial drug compounds as published in both journal and patent literature. Owing to the vast number of potential structures, we have concentrated only on those drugs containing five-membered heterocycles and focused principally on the assembly of the heterocyclic core. In order to target the most representative chemical entities, the examples discussed have been selected from the top 200 best-selling drugs of recent years. This article was authored by Marcus Bauman, Ian R. Baxendale, Stephen D. Lay, and others.