A study of the trade in medicinal plants in the Eastern Cape Province of South Africa undertook to document the species traded, to determine the quantities harvested annually, and to assess the economic value of the trade. All the participants involved at the different levels of the trade were included in the survey, that is, informal street hawkers, owners of amayeza esiXhosa stores, traditional healers, and consumers of traditional medicines. In total, 282 questionnaires were administered in six urban centres. It was found that poorly educated black middle-aged women of low economic standing dominate the trade. A minimum of 166 medicinal plant species were traded at the study sites alone, providing 525 tonnes of plant material valued at approximately R27 million annually. Plants were harvested from a diverse range of vegetation types including Valley Thicket, Afromontane Forest, Coastal Forest and Moist Upland Grassland, the most frequently sold species differing significantly from those documented in similar studies in other regions. The Forest Biome was the vegetation type found to be most threatened by over-harvesting. Of the species documented, 93% were being harvested unsustainably and 34 species have been prioritised for conservation management