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Global climate change is predicted to increase heat, drought, and soil-drying conditions, and thereby increase crop sensitivity to water vapour pressure deficit, resulting in productivity losses. Increasing competition between agricultural freshwater use and municipal or industrial uses suggest that crops with greater heat and drought durability and greater water-use efficiency will be crucial for sustainable biomass production systems in the future. Agave (Agavaceae) and Opuntia (Cactaceae) represent highly water-use efficient bioenergy crops that could diversify bioenergy feedstock supply yet preserve or expand feedstock production into semi-arid, abandoned, or degraded agricultural lands, and reclaim drylands. Agave and Opuntia are crassulacean acid metabolism species that can achieve high water-use efficiencies and grow in water-limited areas with insufficient precipitation to support traditional C-3 or C-4 bioenergy crops. Both Agave and Opuntia have the potential to produce above-ground biomass rivalling that of C-3 and C-4 crops under optimal growing conditions. The low lignin and high amorphous cellulose contents of Agave and Opuntia lignocellulosic biomass will be less recalcitrant to deconstruction than traditional feedstocks, as confirmed by pretreatments that improve saccharification of Agave. Refined environmental productivity indices and geographical information systems modelling have provided estimates of Agave and Opuntia biomass productivity and terrestrial sequestration of atmospheric CO2; however, the accuracy of such modelling efforts can be improved through the expansion of field trials in diverse geographical settings. Lastly, life cycle analysis indicates that Agave would have productivity, life cycle energy, and greenhouse gas balances comparable or superior to those of traditional bioenergy feedstocks, but would be far more water-use efficient.