In response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC prepared for the potential introduction of Ebola into the United States. The immediate goals were to rapidly identify and isolate any cases of Ebola, prevent transmission, and promote timely treatment of affected patients. CDC's technical expertise and the collaboration of multiple partners in state, local, and municipal public health departments; health care facilities; emergency medical services; and U.S. government agencies were essential to the domestic preparedness and response to the Ebola epidemic and relied on longstanding partnerships. CDC established a comprehensive response that included two new strategies: 1) active monitoring of travelers arriving from countries affected by Ebola and other persons at risk for Ebola and 2) a tiered system of hospital facility preparedness that enabled prioritization of training. CDC rapidly deployed a diagnostic assay for Ebola virus (EBOV) to public health laboratories. Guidance was developed to assist in evaluation of patients possibly infected with EBOV, for appropriate infection control, to support emergency responders, and for handling of infectious waste. CDC rapid response teams were formed to provide assistance within 24 hours to a health care facility managing a patient with Ebola. As a result of the collaborations to rapidly identify, isolate, and manage Ebola patients and the extensive preparations to prevent spread of EBOV, the United States is now better prepared to address the next global infectious disease threat.The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).