In Africa, herbal medicines are often used as primary treatment for HIV/AIDS and for HIV-related problems. In general, traditional medicines are not well researched, and are poorly regulated. We review the evidence and safety concerns related to the use of two specific African herbals, which are currently recommended by the Ministry of Health in South Africa and member states for use in HIV: African Potato and Sutherlandia. We review the pharmacology, toxicology and pharmacokinetics of these herbal medicines. Despite the popularity of their use and the support of Ministries of Health and NGOs in some African countries, no clinical trials of efficacy exist, and low-level evidence of harm identifies the potential for drug interactions with antiretroviral drugs. Efforts should be made by mainstream health professionals to provide validated information to traditional healers and patients on the judicious use of herbal remedies. This may reduce harm through failed expectations, pharmacologic adverse events including possible drug/herb interactions and unnecessary added therapeutic costs. Efforts should also be directed at evaluating the possible benefits of natural products in HIV/AIDS treatment.The use of traditional medicine and Natural Health Products is widespread among those living with HIV infection [1]. Many patients take a broad range of natural health products (NHPs) in addition to their conventional therapeutic products [2][3][4]. In Africa, traditional herbal medicines are often used as primary treatment for HIV/AIDS and for HIV-related problems including dermatological disorders, nausea, depression, insomnia, and weakness [2,[5][6][7][8]. Some herbal and traditional medicines are not well-researched, poorly regulated, may contain adulterated products, and may produce adverse effects [8][9][10][11][12][13]. Notwithstanding these concerns, the use of traditional medicines by Africans living with HIV is believed to be widespread, although insufficiently documented [14][15][16].Despite a paucity of evidence on effectiveness, and the possibility of harm, the Ministries of Health of several African nations currently promote traditional medicines for the treatment of HIV and associated symptoms [12,17]. In the case of South Africa, the Ministry of Health is actively promoting the use of traditional medicines with antiretroviral treatments [18]. Two principal African herbal compounds used for HIV/ AIDS treatment in sub-Saharan Africa include Hypoxis hemerocallidea (common name: African potato), and Sutherlandia. These two herbal remedies are currently recommended by the South African Ministry of Health for HIV management [17]. The 14 member states of the South African Development Community (SADC) which includes Angola, Botswana, Democratic Republic of Congo, Lesotho, Malawi, Mauritius, Mozambique, Namibia, Seychelles, South Africa, Swaziland, Tanzania, Zambia, and Zimbabwe, also support their use [19]. Responding to the compelling need for evidence regarding traditional medicines, we reviewed the current ...