In the central Andes of South America, a combination of crustal shortening and thickening, lithospheric densification and delamination, and surficial and climate interactions have resulted in development of the 3–5 km-high central Andean plateau and flanking 6–7 km peaks of the Eastern and Western cordilleras. Questions remain concerning the timing and rate of surface uplift and the relative roles of these mechanisms in producing and supporting these extreme elevations. End-member models attempting to answer these questions propose either a large-magnitude, rapid late Miocene uplift event, or rather slow and steady topographic growth initiating in the late Oligocene–early Miocene. The former model is based primarily on climate- and temperature-sensitive stable isotope analysis of carbonate material as a paleo-elevation proxy and is consistent with an uplift mechanism involving large-scale delamination and foundering of negatively buoyant lower crust and mantle lithosphere. The latter model is consistent with surface uplift driven directly by crustal shortening and is supported by climate simulations that suggest a nonlinear climate response to topographic uplift, indicating instead that there are threshold changes in temperature and isotopic composition of precipitation with rising topography, and highlighting that the use of such proxies may overestimate uplift rate and magnitude.