The unabated rise in health care costs is bringing health services research into center stage as an applied science to help guide health care managers, purchasers, and regulators. To be equal to the task, health services research must pursue at least four intellectual agendas: the study of efficacy (knowing what works), the study of appropriateness (using what works), the study of the execution of care (doing well what works), and the study of the purposes of care (the values that underlie action). The responsibility for the financing and conduct of the research agendas varies with the level of aggregation of data and effort needed for each topic. All four topics must be pursued effectively if health care quality is to be successfully defined, measured, and protected.