The Alliance of Bioversity International and CIAT curates the world’s largest cassava (Manihot esculenta Crantz) germplasm collection, held at its Future Seeds genebank in Cali, Colombia. Since first collection expeditions in 1969, a primary focus was to assemble and conserve the diversity from the crop’s center of origin in the American tropics. Later additions expanded representation from Asia and Africa as secondary centers of diversity. The collection consists mainly of landraces (about 5000 accessions), bred lines from CIAT (375) and from partner institutions (253), and related wild Manihot (377 accessions from 23 species or subspecies). Secure conservation, first as a field collection and then in a slow-growth in vitro system, gave priority to pathogen testing and methods to assure successful clonal propagation over many generations. Cryopreservation research is ongoing to achieve additional security and efficiency. CIAT extensively characterized accessions through morphological, biochemical and molecular criteria. As a core goal, the collection has been a foundation for genetic improvement of the crop globally. The paper provides perspectives on the future management and use of the collection in the context of the recently established Future Seeds genebank facilities at CIAT, and new tools and technologies that support more effective conservation, evaluation and use.