In late 2004, the British government decided to allow a lipid-lowering agent to be sold as an over-the-counter medication. In contrast, the U.S. Food and Drug Administration recently decided not to do so. The United States and other countries will soon face similar decisions for other statins. Although statins have infrequent side effects and have been shown to be effective in moderate-risk primary prevention populations, many questions remain unanswered about their effectiveness at lower doses in over-the-counter use, the ability of patients to self-select themselves for appropriate therapy, and the social and economic implications associated with this method of distribution for preventive medications. A rational policy decision concerning over-the-counter statin use will require an effectiveness trial to provide data on how such drugs would be used in this context, as well as on the clinical outcomes that could be expected from this novel "route of administration."