Since the late Miocene an ignimbrite flare-up has resulted in a major volcano-tectonic province, the Altiplano-Puna volcanic complex, in the lat 21° to 24°S part of the Central Volcanic Zone of the Andes. The dominant elements of the complex, which defines an area of about 50000 km2 between the Atacama basin and the Altiplano, are several large nested caldera complexes which are the source structures for the major regionally distributed ignimbrite sheets that characterize the complex. The chemical and physical characteristics of these ignimbrites are best reconciled with an origin by large-scale crustal melting. The timing of the ignimbrite flare-up coincides well with thickening of the Central Volcanic Zone crust just prior to the late Miocene, and the coincidence of the Altiplano-Puna volcanic complex with the thickest part of this crust (∼70 km) points to a cause and effect relation. Crustal melting in response to crustal thickening and the heat input from subduction-related magmas is suggested to have resulted in large-scale sificic magmatism. Diapiric uprise of these magmas into a zone of tectonically weakened crust due to strike-slip tectonics associated with the Atacama basin resulted in major ignimbrite eruptions and the formation of the calderas of the Altiplano-Puna volcanic complex.