BACKGROUND AND SCOPE: Crassulacean acid metabolism (CAM) is an intriguing physiological adaptation in plants that are widespread throughout many ecosystems. Despite the relatively recent mechanistic understanding of CAM in plant physiology, evidence from historical records suggests that ancient cultures in the Americas also recognized the value of CAM plants. Agave species, in particular, have a rich cultural legacy that provides a foundation for commercially valued products. Here, we review that legacy and potential relationships between ancient values and the needs of modern-day climate adaptation strategies. CONCLUSIONS: There are many products that can be produced from Agave species, including food, sugar, fibre and medicines. Traditional knowledge about agricultural management and preparation of plant products can be combined with new ecophysiological knowledge and agronomic techniques to develop these resources in the borderland region of the southwestern USA and Mexico. Historical records of pre-Columbian practices in the Sonoran desert and remnants of centuries-old agriculture in Baja California and Sonora demonstrate the climate resilience of Agave agriculture. Commercial growth of both tequila and bacanora indicates the potential for large-scale production today, but also underscores the importance of adopting regenerative agricultural practices to accomplish environmentally sustainable production. Recent international recognition of the Appellation of Origin for several Agave species produced for spirits in Mexico might provide opportunities for agricultural diversification. In contrast, fibre is currently produced from several Agave species on many continents. Projections of growth with future climate change suggest that Agave spp. will be viable alternatives for commodity crops that suffer declines during drought and increased temperatures. Historical cultivation of Agave affirms that these CAM plants can supply sugar, soft and hard fibres, medicines and food supplements.