Flavaglines constitute a distinctive family of plant metabolites isolated from medicinal plants of the genus Aglaia. These compounds exhibit a broad spectrum of distinctive pharmacological properties, including anti-inflammatory, neuroprotective, cardioprotective, and anticancer activities. These natural cyclopenta[b]benzofurans are characterized by densely functionalized tricyclic frameworks, as exemplified by the structures of rocaglamide or silvestrol, which makes them extremely attractive targets for total synthesis, in addition to their therapeutic potential. In this review we describe the various synthetic approaches to the total synthesis of flavaglines, culminating in a new generation of diastereo- and enantioselective total syntheses.