An estimated 5.7 million people were living with HIV and AIDS in South Africa in 2009, more than in any other country. Up to 90% of all HIV/AIDS patients develop opportunistic fungi infections (OFIs) at some point during the course of the disease and 10 to 20% dies as a direct consequence of these. Despite the broad use of medicinal plants in South Africa, there is a dearth of knowledge regarding the use of such plants in the management of opportunistic fungal infections in HIV/AIDS patients. Knowledge of these plants is very important as this can serve as leads in the discovery of new antifungal agents. The purpose of this study was to document the indigenous knowledge of medicinal plants used in the management of opportunistic fungal infections in HIV/AIDS patients in the Eastern Cape, South Africa. Information was obtained through conversations with traditional healers and AIDS patients with the aid of semi-structured questionnaires, direct observations and by reviewing studies reported in the literature. A total of 123 informants participated in the study, including 22 (21.8%) traditional healers and 101 (78.2%) HIV/AIDS patients. Thirty two plant species distributed in 26 families and 32 genera were identified as being used to treat one or more of the OFIs. Considering the widespread use of these medicinal plants to treat various ailments and their current use in the management of oportunistic fungal infections in HIV/AIDS patients, it therefore becomes crucial to scientifically validate the therapeutic uses and safety of these plants through phytochemical screening, antifungal susceptibility tests and toxicological studies.