When do physicians know enough about the beneficial effects of a new medical intervention to start recommending or using it? When is the available information about harmful adverse effects sufficient to conclude that the risks outweigh the potential benefits? If in doubt, should physicians err on the side of caution or on the side of hope? These questions are at the core of all medical decision making. It is a complicated process because medical knowledge is typically incomplete and ambiguous. It is especially complex to make decisions about whether to use drugs that may prevent disease in the future, particularly when these drugs are given to otherwise healthy individuals. Vaccines are examples of such drugs, and the human papillomavirus (HPV) vaccine is a case in point.