The Andes make up the largest orogenic system developed by subduction of oceanic crust along a continental margin. Subduction began soon after the breakup of Rodinia in Late Proterozoic times, and since that time, it has been intermittently active up to the present. The evolution of the Pacific margin of South America during the Paleozoic occurred in the following stages: (1) initial Proterozoic rifting followed by subduction and final re-amalgamation of the margin in Early Cambrian times, as depicted by the Puncoviscana and Tucavaca Basins and related granitoids in southern Bolivia and northern Argentina; (2) a later phase of rifting in the Middle Cambrian, and subsequent collisions in Middle Ordovician times of parautochthonous terranes derived from Gondwana, such as Paracas, Arequipa, and Antofalla, and exotic terranes originating in Laurentia, such as Cuyania, Chilenia and Chibcha; (3) final Permian collision between South America and North America to form Pangea during the Alleghanides orogeny, leaving behind rifted pieces of Laurentia as the Tahami and Tahuin terranes in the Northern Andes and other poorly known orthogneisses in the Cordillera Real of Ecuador in the Late Permian–Early Triassic; and (4) amalgamation of the Mejillonia and Patagonia terranes in Early Permian times, representing the last convergence episodes recorded in the margin during the Gondwanides orogeny. These rifting episodes and subsequent collisions along the continental margin were the result of changes of the absolute motion of Gondwana related to global plate reorganizations during Proterozoic to Paleozoic times. Generalized rifting during Pangea breakup in the Triassic concentrated extension in the hanging wall of the sutures that amalgamated the Paleozoic terranes. The opening of the Indian Ocean in Early Jurassic times was associated with a new phase of subduction along the continental margin. The northeastward absolute motion of western Gondwana produced a negative trench roll-back velocity that controlled subduction under an extensional regime until late Early Cretaceous times. The Northern Andes of Venezuela, Colombia, and Ecuador record a series of collisions of island arcs and oceanic plateaus from the Early Cretaceous to the middle Miocene as a result of interaction with the Caribbean plate. The remaining Central and Southern Andes record periods of orogenesis and mountain building alternating with periods of quiescence and absence of deformation as recorded in parts of the Oligocene. Based on the generalized occurrence of flat-slab subduction episodes through time, as recorded in most of the Andean segments in Cenozoic and older times, this paper presents a conceptual orogenic cycle that accounts for the sequence of quiescence, minor arc magmatism, expansion and migration of the volcanic fronts, deformation, subsequent lithospheric and crustal delamination, and final foreland fold-and-thrust development. These episodes are related to shallowing and steepening of the subduction zones through time. This conceptual cycle, similar to the Laramide orogeny in North America, may be recognized wherever a subduction system is or was active in a continental margin.