Return on investment (ROI) is an economic measure used to indicate how much economic benefit is derived from a program in relation to its costs. Interest in the use of ROI in public health has grown substantially over recent years. Given its potential influence on resource allocation, it is crucial to understand the benefits and the risks of using ROI to defend public health programs. In this paper, we explore those benefits and risks. We present two recent examples of ROI use in public health in the United States and Canada and conclude with a series of proposals to minimize the risks associated with using ROI to defend public health interventions.