The five-membered oxacyclic system of furan-2(5H)-ones, commonly named as γ- butenolides or appropriately as Δ<sup>α,β</sup>-butenolides, is of high interest since many studies have proven its bioactivity. During the past few years, Δ<sup>α,β</sup>-butenolides have been important synthetic targets, with several reports of new procedures for their construction. A short compendium of the main different synthetic methodologies focused on the Δ<sup>α,β</sup>-butenolide ring formation, along with selected examples of compounds with relevant biological activities of these promising pharmaceutical entities is presented.