Ethnobotany has been, for too long, a descriptive discipline. However, ethnobotanists are increasingly calling for a paradigm shift towards the formulation of unifying theories and hypothesis-driven research in ethnobotany. Here, we formulated a theory, termed time-since-introduction theory, to explain the integration of alien plants into local pharmacopoeias in their recipient environment. This theory suggests that the factor time is paramount in determining which alien plants are more likely to be included in the medicinal flora of the areas they are introduced in. The theory relies on three hypotheses, the availability and versatility hypotheses alongside the residence time hypothesis newly proposed in the present study. We tested this theory by fitting a structural equation model to ethnobotanical data collected on South Africa’s alien woody flora. Although residence time is a direct predictor of medicinal status of alien plants, it is a better predictor when mediated through plant versatility. These findings are in support of the theory, and we consequently proposed a framework with which to understand different paths linking all three hypotheses. Collectively, our study shows the value of time in the development of ethnobotanical knowledge and fully responds to the pressing call for paradigm shift in ethnobotany.