Background Aloe vera supports a substantial global trade yet its wild origins, and explanations for its popularity over 500 related Aloe species in one of the world’s largest succulent groups, have remained uncertain. We developed an explicit phylogenetic framework to explore links between the rich traditions of medicinal use and leaf succulence in aloes. Results The phylogenetic hypothesis clarifies the origins of Aloe vera to the Arabian Peninsula at the northernmost limits of the range for aloes. The genus Aloe originated in southern Africa ~16 million years ago and underwent two major radiations driven by different speciation processes, giving rise to the extraordinary diversity known today. Large, succulent leaves typical of medicinal aloes arose during the most recent diversification ~10 million years ago and are strongly correlated to the phylogeny and to the likelihood of a species being used for medicine. A significant, albeit weak, phylogenetic signal is evident in the medicinal uses of aloes, suggesting that the properties for which they are valued do not occur randomly across the branches of the phylogenetic tree. Conclusions Phylogenetic investigation of plant use and leaf succulence among aloes has yielded new explanations for the extraordinary market dominance of Aloe vera. The industry preference for Aloe vera appears to be due to its proximity to important historic trade routes, and early introduction to trade and cultivation. Well-developed succulent leaf mesophyll tissue, an adaptive feature that likely contributed to the ecological success of the genus Aloe, is the main predictor for medicinal use among Aloe species, whereas evolutionary loss of succulence tends to be associated with losses of medicinal use. Phylogenetic analyses of plant use offer potential to understand patterns in the value of global plant diversity.