Changing threats to the public’s health necessitate a profound transformation of the public health enterprise. Despite recent attention to the biodefense role of public health, policymakers have not developed a clear, realistic vision for the structure and functionality of the governmental public health system. Lack of leadership and organizational disconnects across levels of government have prevented strategic alignment of resources and undermined momentum for meaningful change. A transformed public health system is needed to address the demands of emergency preparedness and health protection. Such transformation should include focused, risk-based resource allocation; regional planning; technological upgrades; workforce restructuring; improved integration of private-sector assets; and better performance monitoring.