BACKGROUND Harpagophytum procumbens subps. procumbens (Burch.) DC. ex Meisn. (Pedaliaceae) is an important traditional medicine growing in the Kalahari region of southern Africa where it is consumed as a general health tonic and for treating diverse ailments including arthritis, pain, fever, ulcers and boils. OBJECTIVE To provide a comprehensive overview of the ethnobotany, phytochemistry and biological activity of H. procumbens and possibly make recommendations for further research. METHODS Peer-reviewed articles on H. procumbens were acquired on Scopus, ScienceDirect and SciFinder, there was no specific timeline set for the search. A focus group discussion was held with different communities in Botswana to further understand ethnobotanical uses of the plant. RESULTS Harpogophytum procumbens is used for a wide variety of health conditions in the form of infusions, decoctions, tinctures, powders and extracts. In addition to the common local use for arthritis and pain, other ethnomedicinal uses include dyspepsia, fever, blood diseases, urinary tract infections, postpartum pain, sprains, sores, ulcers and boils. Scientific studies revealed that H. procumbens exhibits analgesic, anti-oxidant, anti-diabetic, anti-epileptic, antimicrobial and antimalarial activities amongst others. Iridoid glycosides and phenylpropanoid glycosides have been the focus of phytochemical investigations as the biological activity has been ascribed to the iridoid glycosides (such as harpagoside and harpagide), which are common in nature and are known to possess anti-inflammatory activity. In addition, it has been shown that the hydrolysed products of harpagoside and harpagide have more pronounced anti-inflammatory activity when compared to the unhydrolysed compounds. Harpagophytum zeyheri is a close taxonomic ally of H. procumbens but H. procumbens is the favoured species of commerce, and contains higher levels of the pharmacologically active constituents. The two are used interchangeably and H. procumbens raw material is often intentionally adulterated with H. zeyheri and this may impact on the efficacy of inadequately controlled health products. The main exporter of this highly commercialised plant is Namibia. In 2009 alone, Harpagophytum exports were worth approximately €1.06 million. The high demand for health products based on this plant has led to over-harvesting, raising concerns about sustainability. Although only the secondary tubers are utilised commercially, the whole plant is often destroyed during harvesting. CONCLUSIONS Harpagophytum procumbens is used to treat a wide range of ailments. Some of the ethnobotanical claims have been confirmed through in vitro studies, however, when the constituents deemed to be the biologically active compounds were isolated the efficacy was lower than that of the whole extract. This necessitates the use of a different approach where all the metabolites are considered using a robust method such as spectroscopy; the phytochemical data can then be superimposed on the biological activity. Furthermore, there is a need to develop rapid and efficient quality control methods for both raw materials and products because the orthodox methods in current use are time-consuming and labour intensive.