A major, comprehensive, system-wide quality improvement strategy for healthcare was launched in Mexico in January, 2001, for a six-year period. This strategy was one of the key components of a health reform initiated by a new Government that took office in December, 2000. This strategy, called the National Crusade for Quality in Healthcare, encompassed several interventions aimed at improving technical and interpersonal quality. This chapter summarizes each of these interventions and reflects on some lessons learned. The main messages are that the sum of quality improvements of individual healthcare providers, processes or even units, is not necessarily equal to the quality of the whole system, that in order to improve quality system-wide it is necessary to design a comprehensive strategy, and that this is possible in a middle-income country.