Aloe, the largest genus in the Asphodelaceae family, comprises 548 species, with A. vera, A. arborescens and A. ferox being among the most widely studied species. Aloe species originated in arid climates and cover various habitats, from sea level up to 2700 m, and from desert to closed-canopy forests. For human health, Aloe species are the richest natural sources. The biological activity of Aloe sp. constituents covers a wide spectrum. Most of the indications come from traditional, folkloric use and several have been verified by in vitro or in vivo studies. Emodin, the main phenolic component, has showed anti-neoplastic, anti-inflammatory, anti-angiogenic and toxicological potential for use in pharmacology. Polysaccharides, with acemannan being the most important, are present in high abundance in Aloe gels. Acemannan has been reported to have applications in oral, metabolic and cardiovascular diseases, oncology, dentistry and wound healing. The effectiveness of Aloe sp. constituents on colon, liver, duodenum, skin, pancreas, intestine, lungs and kidneys cancers was highly studied with remarkable findings. Regarding the metabolic syndrome, Aloe sp. can be used as an antidiabetic and reduces cholesterol and total body fat. Constituents of Aloe sp. are nontoxic in experimental acute oral studies and are widely used in cosmetology and as bitter agents or consistence modifiers in food and beverages. Traditional Aloe remedies cover most human diseases; however, in order to gain legitimacy, the Aloe-derived drugs must have a well-established composition, with thoroughly investigated adverse effects and conventional drug interactions.