This paper explores the challenges and opportunities associated with the evaluation of treatments arising from traditional medical systems (TMS). Globalization and popular consumer-and industry-driven market forces contribute to the spread of traditional treatments, techniques and technologies, but do not necessarily ensure their usefulness or safety. The international scientific community is obliged to evaluate the safety and efficacy of these treatments because of their potential impact on global public health. Clinical evaluations of traditional treatments, however, have complex methodological and practical challenges, depending on the goals of the research and the audience for the results (country of origin; or new host countries and new patient populations). To address these challenges, the authors offer the following recommendations to identify and prioritize treatments to study and how to design study protocols. Evaluations of traditional treatments are best addressed first by collaborative, international, pragmatic studies. Protocols for observational, prospective, pragmatic pilot study (randomized and controlled, when feasible) should be designed collaboratively and executed simultaneously in the culture of origin and in new contexts. This, in turn, could determine the acceptability, usefulness and feasibility of larger randomized controlled trials (RCTs). International multicentre RCTs would have the potential benefits of evaluating safety and effectiveness and also assessing the transferability of a traditional treatment across social and cultural contexts.