Some drugs eventually have to be removed from the market because of a negative benefit-to-harm ratio, including an excess of mortality. Drug safety is the result of multiple factors, commencing with how clinical trials are designed, the information generated by and/or hidden through these trials, trial analysis by drug regulatory authorities (DRAs) and the amount of information that DRAs choose to release, the amount of published information regarding drug safety, the effectiveness of postmarket surveillance systems in recognizing and reporting adverse drug reactions, and the structure of DRAs such as the United States Food and Drug Administration and its equivalent in other countries. This commentary will look at each of these issues in order to highlight the problems in the current approach to drug safety and finally indicate how some of these deficiencies should be addressed.