Celastraceae plant extracts have been widely used as traditional medicines and insecticides in China and South America. More recently, the extracts from Celastraceae plants have been studied at the molecular level and many of the interesting medicinal and agrochemical properties can be attributed to a large class of sesquiterpene alkaloids found in these extracts. These are generally based on highly oxygenated dihydroagarofuran cores with pyridyl diacid macrodilactone bridging ligands. Whereas previous reviews have focused on the dihydroagarofuran cores, in this article, the history, structure, and syntheses of the macrodilactone bridging ligands are reviewed.