The 6-alkyl-2,4-dihydroxybenzoate moiety known commonly as resorcylate occurs widely as a building block in various fused cyclic systems of bioactive natural products and analogues. Among these many isolated active molecules, mycophenolic acid (MPA) was one of the most studied for its structural features and its potential biological activity. This perspective article portrays the unique biosynthetic interrelationships of polyketide formations in to resorcylates, which are implemented by recent biomimetic/chemical synthetic investigations of the natural product target. The resorcylate, MPA have remained as interesting targets for total synthesis in many laboratories worldwide. There are 13 syntheses reported for MPA to date (Scifinder search). The synthetic strategies for this potential lead compound was an evolution of various methods from generating the highly-substituted aromatic system via employing simple and commercially available materials to the catalytic methods employed which always involve linear sequences; convergent approaches to the most important protecting group-free syntheses are also briefly documented in this critical review. This natural product has been the subject of considerable synthetic study. Most reported total syntheses employ 6-alkyl-2,4-hydroxybenzoic acids (lactones) as intermediates and proceed via stepwise derivatization to introduce other functionalities.