Quaternary-Recent volcanism in the Andes has occurred in three regions: 45–33°S, 28–16°S and 2°S–5°N, each of which has a distinct plate tectonic setting and contains volcanic suites with different chemical and isotopic characteristics. Isotope ratios of O and Sr are lowest and those of Pb least variable in the southern volcanic zone (SVZ) where medium-K lavas have isotopic characteristics equivalent to volcanics from intraoceanic arcs where continental crust is absent. The SVZ lavas were probably derived from an asthenospheric mantle source above a shallow Benioff zone. Parental basaltic magmas rose largely unmodified through thin continental crust, where differentiation occurred by low-pressure crystal fractionation without concurrent modification of isotopic composition. The slight enrichment of 206Pb in the northern volcanic zone (NVZ), where the crust is thin and the Benioff zone deep, suggests a greater subduction-zone component for parental medium-K magmas. The slight 18O enrichment suggests a small amount of lower crustal interaction. Isotope ratios of O and Sr are highest and those of Pb most variable in the central volcanic zone (CVZ). Parental magmas in the CVZ were probably generated within the same mantle source region as those in the SVZ and NVZ. Subsequently, during transit through the exceptionally thick continental crust of the central Andes, high-K magmas were produced by a combination of bulk contamination in the lower crust and later low-pressure fractional crystallization-assimilation processes in the upper crust which altered both chemical and isotopic compositions.