The Agave genus includes over 299 accepted species, and Mexico hosts ca of 80% of these species. Historically, Agaves have been important sources of food and fiber and have been used to produce a variety of alcoholic beverages. The production of these drinks involves removing the plant’s apical meristems, which prevents flower and seed formation, and disrupts pollination, thereby impacting the Agave species’ genetic diversity and ecological dynamics. A recent increase in global demand for mezcal and tequila has led to the overexploitation of wild Agave populations, as well as the expansion of monoculture plantations of clonally propagated plants, further affecting genetic variation. Understanding the genetic changes resulting from Agave management is essential for assessing genetic resources and developing conservation strategies. Genomic tools such as RADseq (Restriction-site associated DNA sequencing), have been used to study the genetic diversity of different mezcal-producing species, showing, in general, high levels of genetic variation, except in Agave tequilana (which has lower levels). It is discussed how genomic diversity is distributed across different Agave species, proposing potential conservation genetics and management measures, and how global climatic change will further impact these mezcal-producing Agave species.