The Great Pyramid of Cholula is both the largest and oldest continuously occupied building in Mesoamerica. Initial occupation of the ceremonial precinct began in the Late Formative period, and the first building stage of the pyramid dates to the Terminal Formative. The Great Pyramid was built in four major construction stages and at least nine minor modifications. Early stages shared stylistic similarities with Teotihuacan, but toward the end of its construction history external contacts shifted to the Gulf Coast, particularly El Tajin, and probably relate to occupation by ethnic Olmeca-Xicallanca. The fourth and final stage was contemporary with extensive construction on the south side at the Patio of the Altars, and dates to the Early Postclassic period. This period ended, however, with the partial abandonment of the pyramid when ethnic Tolteca-Chichimeca constructed a ceremonial center around their “new” Pyramid of Quetzalcoatl. The Great Pyramid continued as an important shrine dedicated to mountain worship and a rain deity until the Spanish Conquest. It remains one of the most important religious sites in Mexico, where the shrine of the Virgin of the Remedies attracts pilgrims to the church atop the pyramid mound during the annual festival. This paper summarizes the archaeological and ethnohistorical information available to reinterpret the construction history and ideological content of the pyramid throughout its long existence.