The most exciting scientific progress occurs when new research challenges conventional wisdom. Even when a medical practice is founded on less-than-perfect scientific data, testing of an established therapy is nearly impossible to justify unless compelling new data lead to questioning of standard care.1 One example is the use of epinephrine, which has been a cornerstone of cardiac resuscitation and advanced cardiac life support since the 1960s. In this issue of JAMA, the report by Hagihara et al, based on one of the largest observational databases of cardiopulmonary resuscitation (CPR) ever assembled, challenges the role of epinephrine drug therapy during cardiac arrest.2 These new data suggest that epinephrine use may be associated with lower survival and worse neurological outcomes after cardiac arrest.