The genus Alepidea is highly valued in traditional medicine across southern Africa, although historical confusion over species names has made it difficult to distinguish them. While A. amatymbica is often cited in literature, closely related species such as A. cordifolia are more widely distributed; from northwestern KwaZulu–Natal to Lesotho, Eswatini, Zimbabwe and Mozambique; and are likely the most used. Several species, including A. cordifolia, A. amatymbica and A. macowanii, are known locally as ikhathazo (Zulu) or inkatazo (Xhosa) and are often used interchangeably. Their underground stems, or rhizomes, are large, aromatic, and resinous, and form the basis of traditional remedies. Rhizomes are used to treat respiratory problems such as coughs, colds, influenza, and asthma, as well as digestive disorders, rheumatism, wounds, sore throats, and malaria. Remedies are prepared as decoctions, infusions, chewing, or inhaling powdered roots, with dosages adapted for children. These rhizomes are widely traded in informal herbal markets across South Africa and Lesotho, reflecting both cultural importance and ongoing demand. Scientific studies have identified kaurene-type diterpenes in Alepidea rhizomes, which have antibacterial, anti-inflammatory, muscle-relaxing, and mild diuretic effects. These compounds likely underpin the traditional uses of the plant and point to potential pharmacological applications. Alepidea species are also used in ethnoveterinary medicine for livestock ailments, and historically for tonics, insect repellents, and other purposes. High demand, combined with destructive harvesting of rhizomes and habitat loss from agriculture and forestry, has caused severe declines in wild populations of related species, with reductions of 50% or more over the past 60 years and local extinctions reported in KwaZulu-Natal, Zimbabwe, and parts of Lesotho. While specific data on Alepidea setifera is limited, it shares many physical and chemical traits with its relatives, suggesting similar uses. Cultivating A. setifera and other Alepidea species could reduce pressure on wild populations, provide a sustainable source of rhizomes, support biodiversity, and create economic opportunities for local communities, helping to preserve both cultural heritage and South Africa’s indigenous plants. High demand for rhizomes, coupled with destructive harvesting, habitat loss, and overcollection, has caused wild populations of related species to decline dramatically. At the same time, informal trade in urban and rural markets highlights an unmet economic potential. Formalizing this trade; through cultivation, sustainable harvesting and quality control, could provide livelihoods, preserve cultural practices, and protect biodiversity. Developing commercial plant-based products is complex, expensive, and regulated, but a dual approach that respects indigenous knowledge while ensuring safety and efficacy through scientific methods offers a realistic path forward.