Aloe L. (Asphodelaceae) is a monocotyledonous group of considerable popularity among succulent plant collectors and with a long history of medicinal use. It comprises ca. 500 species occurring throughout Africa, the Arabian Peninsula and western Indian Ocean islands. The first comprehensive ethnobotanical study of Aloe (excluding the cultivated A. vera) was undertaken using the literature as a surrogate for data gathered by interview methods. Over 1400 use records representing 173 species were collated, the majority (74%) of which described medicinal uses, including species used for natural products. In southern Africa, 53% of approximately 120 Aloe species in the region are used for health and wellbeing. Consensus ratios indicated that the uses of Aloe spp. for medicine and pest control are of the greatest biocultural importance. Utility has contributed to the recognition of diversity, taxonomic complexity, and conservation concerns, in Aloe. A systematic evaluation of the problematic maculate (spotted) species complex, section Pictae, was undertaken. New sequences were acquired of the nuclear ribosomal internal transcribed spacer (ITS), chloroplast trnL intron, trnL–F spacer and matK gene in 29 maculate species of Aloe. A well supported monophyletic (holophyletic) maculate group was recovered in phylogenetic trees of comparable topology generated by parsimony analysis and Bayesian inference. A representative of the related section Paniculatae, A. striata, was recovered in the maculate group, whereas doubtful maculate species with unusual floral morphology (A. leptosiphon and A. suffulta) comprised a sister group. Analogous patterns were identified in chemosystematic and comparative morphological studies of 34 and 36 maculate species, respectively, and insights were gained into interspecific relationships. The flavonoids isoorientin and isovitexin, and a new C-glycosylanthrone, 6′-malonylnataloin, were characterised using hyphenated chromatographic techniques and nuclear magnetic resonance (NMR) spectroscopy. Leaf surface sculpturing, stomata and lobes surrounding the epistomatal pore observed under a scanning electron microscope (SEM) are of potential taxonomic significance. Available evidence indicates that floral characters, namely a basally swollen perianth with constriction above the ovary, are of greater significance than maculate leaves as synapomorphies for section Pictae. An evolutionary hypothesis for section Pictae excludes marginal maculate species with unusual flowers.