Large areas of the tropics and subtropics are too arid or degraded to support food crops, but Agave species may be suitable for biofuel production in these regions. We review the potential of Agave species as biofuel feedstocks in the context of ecophysiology, agronomy, and land availability for this genus globally. Reported dry biomass yields of Agave spp., when annualized, range from <1 to 34 Mg ha−1 yr−1 without irrigation, depending on species and location. Some of the most productive species have not yet been evaluated at a commercial scale. Approximately 0.6 Mha of land previously used to grow Agave for coarse fibers have fallen out of production, largely as a result of competition with synthetic fibers. Theoretically, this crop area alone could provide 6.1 billion L of ethanol if Agave were re-established as a bioenergy feedstock without causing indirect land use change. Almost one-fifth of the global land surface is semiarid, suggesting there may be large opportunities for expansion of Agave crops for feedstock, but more field trials are needed to determine tolerance boundaries for different Agave species.