BACKGROUND: The approach currently used to appraise public health interventions is close to that of health technology appraisal for drugs. This approach is not appropriate for many public health interventions, however, when extremely small individual level benefits are delivered to extremely large populations. In many such situations, randomized controlled trials with sufficient size and power to determine individual level effects are impractical. Such interventions may be cost-effective, even in the absence of traditional evidence to demonstrate this. METHODS: We outline an alternative approach based on decision theory. We apply it to cases where prior beliefs are sufficiently strong and well grounded to allow decision-makers to assume the direction of change of the intervention's outcome, within the context of a transparent and deliberative decision-making process. Decision theory also assumes that decision-makers are risk neutral, implying that they should make decisions based on an intervention's mean cost-effectiveness, and should therefore disregard variance except when deciding to wait for more information. However, they must allow for biases. RESULTS: A framework is presented which has the potential to achieve large health gains at no additional cost. CONCLUSIONS: This analysis provides a rigorous theoretical framework for decision-makers in public health. The implied paradigm shift also applies to some clinically based areas.