There is increased interest in strengthening health systems for developing countries. However, at present, there is common uncertainty about how to accomplish this task. Specifically, several nations are faced with an immense challenge of revamping an entire system. To accomplish this, it is essential to first identify the components of the system that require modification. The World Health Organization (WHO) has proposed health system building blocks, which are now widely recognized as essential components of health systems strengthening.With increased travel and urbanization, the threat of emerging diseases of pandemic potential is increasing alongside endemic diseases such as human immunodeficiency virus (HIV), tuberculosis (TB), malaria, and hepatitis virus infections. At the same time, the epidemiologic patterns are shifting, giving rise to a concurrent increase in disease burden due to non-communicable diseases. These diseases can be addressed by public health surveillance and response systems that are operated by competent public health workers in core public health positions at national and sub-national levels with a focus on disease prevention.We describe two ways that health ministries in developing countries could leverage President Obama's Global Health Initiative (GHI) to build public health surveillance and response systems using proven models for public health systems strengthening and to create the public health workforce to operate those systems. We also offer suggestions for how health ministries could strengthen public health systems within the broad health systems strengthening agenda. Existing programs (e.g., the Global Vaccine Alliance [GAVI] and the Global Fund Against Tuberculosis, AIDS, and Malaria [GFTAM]) can also adapt their current health systems strengthening programs to build sustainable public health systems.