This document discusses non-inferiority trials from the viewpoint of an EU regulator. It outlines the rules for marketing authorizations in the EU, which require that the benefit-risk balance of a new drug be favorable and its therapeutic efficacy substantiated. Non-inferiority trials are common because applicants are not required to show superior benefit-risk over existing therapies. Such trials must demonstrate assay sensitivity and use an appropriate non-inferiority margin to avoid concluding a test drug is equivalent if it is ineffective. Interpreting results as superior, not non-inferior, or non-inferior depends on the statistical analysis. Ethical issues include potential lack of assay sensitivity and enrolling patients in a test drug that may be ineffective