Explicit priority setting presents Mexico with the opportunity to match the pressure and complexity of an advancing epidemiological transition with evidence-based policies driven by a fundamental concern for how to make the best use of scarce resources to improve population health. The Mexican priority-setting experience describes how standardised analytical approaches to decision making, mainly burden of disease and cost-effectiveness analyses, combine with other criteria -eg, being responsive to the legitimate non-health expectations of patients and ensuring fair financing across households- to design and implement a set of three differentiated health intervention packages. This process is a key element of a wider set of reform components aimed at extending health insurance, especially to the poor. The most relevant policy implications include lessons on the use of available and proven analytical tools to set national health priorities, the usefulness of priority-setting results to guide long-term capacity development, the importance of favouring an institutionalised approach to cost-effectiveness analysis, and the need for local technical capacity strengthening as an essential step to balance health-maximising arguments and other non-health criteria in a transparent and systematic process.