The cacao tree, Theobroma cacao L., is cultivated in the tropics, mainly in agroforestry systems, to produce seeds, the valuable raw material for the chocolate industry. Thus, the conservation and use of cacao genetic resources in breeding programs to increase yield and improve quality and disease resistance are vital for the global cacao economy. We review three important topics of cacao genetics essential for sustainable production and crop improvement: (1) geographic distribution of wild cacao populations and geographic patterns of their genetic variation in Amazonia; (2) conservation, availability, and use of cacao genetic resources in cultivar development; (3) genetic basis of agronomic traits, available molecular genetic markers, and genomic resources and their application for cacao improvement. We also highlight critical research areas needed to achieve sustainable cacao cultivation.