To address the threat of the globalization of Rift Valley fever (RVF), a very serious, often fatal, viral disease of domestic animals and humans that occurs throughout sub-Saharan Africa and the Middle East, a team of scientists from the U.S. Department of Agriculture’s Agricultural Research Service (ARS), NASA, the Department of Defense (DOD), and the Centers for Disease Control and Prevention (CDC) developed a highly innovative and effective method to forecast RVF outbreaks based on global climate conditions that determine the local and regional ecological conditions leading to the emergence of the virus in Africa. Using satellite measurements of global and regional elevated sea surface temperatures, and subsequent elevated rainfall and satellite derived-normalized difference vegetation index data, the team developed a model and surveillance system to predict, with lead times of two to four months, specific areas where outbreaks of RVF in humans and animals were expected in the Horn of Africa, Sudan, and Southern Africa at different time periods from September 2006 to February 2009. Predictions were first confirmed by entomological investigations and subsequently by field investigations of virus activity in the areas the team identified by reported cases of RVF in human and livestock populations. The team’s early warning technology was transferred via direct alerts to international and national agricultural and health authorities, websites, and international presentations and publications. The United Nations Food and Agricultural Organization (FAO) and World Health Organization (WHO) issued, for the first time in their history, warnings of an impending RVF outbreak. In response to this international warning, national authorities in Kenya and neighboring countries, and collaborating components of the CDC, DOD, and ARS initiated surveillance activities in risk areas, eventually detecting the virus in mosquitoes in December 2006, weeks prior to subsequent reports of unexplained hemorrhagic fever in humans in this area. Subsequent response and mitigation efforts in at-risk areas included initiation of enhanced surveillance activities, distribution of mosquito nets, dissemination of public information to mobilize social and cultural activities directed at reducing human contact with infected animal products, and implementation of domestic animal vaccination and mosquito control programs. As a result, the number of human and animal cases of RVF that occurred was 10- to 100-fold fewer than previous outbreaks when no early warnings were given.