The objectives of the Global Health Security Agenda (GHSA) will require not only a "One Health" approach to counter natural disease threats against humans, animals, and the environment, but also a security focus to counter deliberate threats to human, animal, and agricultural health and to nations' economies. We have termed this merged approach "One Health Security." It will require the integration of professionals with expertise in security, law enforcement, and intelligence to join the veterinary, agricultural, environmental, and human health experts essential to One Health and the GHSA. Working across such different professions, which occasionally have conflicting aims and different professional cultures, poses multiple challenges, but a multidisciplinary and multisectoral approach is necessary to prevent disease threats; detect them as early as possible (when responses are likely to be most effective); and, in the case of deliberate threats, find who may be responsible. This article describes 2 project areas that exemplify One Health Security that were presented at a workshop in January 2014: the US government and private industry efforts to reduce vulnerabilities to foreign animal diseases, especially foot-and-mouth disease; and AniBioThreat, an EU project to counter deliberate threats to agriculture by raising awareness and implementing prevention and response policies and practices.