 Non-inferiority trials test whether a new experimental treatment is not unacceptably less efficacious than an active control treatment already in use. With continuous improvements in health technologies, standard care, and clinical outcomes, the incremental benefits of newly developed treatments may be only marginal over existing treatments. Sometimes assigning patients to a placebo is unethical. In such circumstances, there has been increasing emphasis on the use of non-inferiority trial designs. Non-inferiority trials are more complex to design, conduct, and interpret than typical superiority trials. This paper reviews the concept of non-inferiority trials and discusses some important issues related to them. This article was authored by Seo Kyung-hwan.