While the appeal of conducting trials in the global setting has never been stronger, global trials also pose daunting challenges to many major aspects of clinical trials, including, but not limited to, design, conduct, analysis, ethics, law and regulation. At the design stage, trialists need to carefully consider many key design aspects, including the potential impact of ethnic diversity on the risk-benefit assessment, the worldwide differences in ethical practices, medical standards of care, research infrastructure, access to care, and legal and regulatory requirements. A solid understanding of these aspects will be essential to the county / site selection process for a global trial. For example, when either the prognosis of the disease under study or the risk-benefit assessment of an experimental medicine is expected to be dependent on ethnicity, trials will need to be designed to ensure that a sufficient number of patients within each ethnical group are enrolled to adequately quantify the impact of ethnicity on trial results. Carefully designed feasibility studies will need to be conducted in all potential regions to evaluate these key design aspects.