A health policy decision often requires a balancing of risks, costs, and benefits. In this paper we illustrate that there is no uniform answer in the United States to the question of who decides the risk-benefit balance. We use a wide range of case examples from medicine and public health to show the different approaches that are used to allocate decision-making responsibility. Our ultimate purpose is to urge the U.S. health policy community to develop a more consistent way of thinking about how risk-benefit decisions could be guided by general principles.