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