The United States faces serious public health threats from the deliberate use of weapons of mass destruction (WMD)--chemical, biological, radiological, or nuclear (CBRN)--by hostile States or terrorists, and from naturally emerging infectious diseases that have a potential to cause illness on a scale that could adversely impact national security. Effective strategies to prevent, mitigate, and treat the consequences of CBRN threats is an integral component of our national security strategy. To that end, the United States must be able to rapidly develop, stockpile, and deploy effective medical countermeasures to protect the American people. The HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) has taken a holistic, end-to-end approach that considers multiple aspects of the medical countermeasures mission including research, development, acquisition, storage, maintenance, deployment, and guidance for utilization. Phase one of this approach established the HHS PHEMCE Strategy for Chemical, Biological, Radiological, and Nuclear Threats (HHS PHEMCE Strategy). The HHS PHEMCE Strategy, published in the Federal Register on March 20, 2007, described a framework of strategic policy goals and objectives for identifying medical countermeasure requirements and establishing priorities for medical countermeasure evaluation, development and acquisition. These strategic policy goals and objectives were used to establish the Four Pillars upon which this HHS Public Health Emergency Medical Countermeasures Enterprise Implementation Plan (HHS PHEMCE Implementation Plan) is based. The HHS PHEMCE Implementation Plan considers the full spectrum of medical countermeasures-related activities, including research, development, acquisition, storage/maintenance, deployment, and utilization. The HHS PHEMCE Implementation Plan is consistent with the President's Biodefense for the 21st Century and is aligned with the National Strategy for Medical Countermeasures against Weapons of Mass Destruction.