Mexico is reaching universal health coverage in 2012. A national health insurance programme called Seguro Popular, introduced in 2003, is providing access to a package of comprehensive health services with financial protection for more than 50 million Mexicans previously excluded from insurance. Universal coverage in Mexico is synonymous with social protection of health. This report analyses the road to universal coverage along three dimensions of protection: against health risks, for patients through quality assurance of health care, and against the financial consequences of disease and injury. We present a conceptual discussion of the transition from labour-based social security to social protection of health, which implies access to effective health care as a universal right based on citizenship, the ethical basis of the Mexican reform. We discuss the conditions that prompted the reform, as well as its design and inception, and we describe the 9-year, evidence-driven implementation process, including updates and improvements to the original programme. The core of the report concentrates on the effects and impacts of the reform, based on analysis of all published and publically available scientific literature and new data. Evidence indicates that Seguro Popular is improving access to health services and reducing the prevalence of catastrophic and impoverishing health expenditures, especially for the poor. Recent studies also show improvement in effective coverage. This research then addresses persistent challenges, including the need to translate financial resources into more effective, equitable and responsive health services. A next generation of reforms will be required and these include systemic measures to complete the reorganisation of the health system by functions. The paper concludes with a discussion of the implications of the Mexican quest to achieve universal health coverage and its relevance for other low-income and middle-income countries.