Zika virus has rapidly spread through the World Health Organization's Region of the Americas since being identified in Brazil in early 2015. Transmitted primarily through the bite of infected Aedes species mosquitoes, Zika virus infection during pregnancy can cause spontaneous abortion and birth defects, including microcephaly (1,2). New York City (NYC) is home to a large number of persons who travel frequently to areas with active Zika virus transmission, including immigrants from these areas. In November 2015, the NYC Department of Health and Mental Hygiene (DOHMH) began developing and implementing plans for managing Zika virus and on February 1, 2016, activated its Incident Command System. During January 1-June 17, 2016, DOHMH coordinated diagnostic laboratory testing for 3,605 persons with travel-associated exposure, 182 (5.0%) of whom had confirmed Zika virus infection. Twenty (11.0%) confirmed patients were pregnant at the time of diagnosis. In addition, two cases of Zika virus-associated Guillain-Barré syndrome were diagnosed. DOHMH's response has focused on 1) identifying and diagnosing suspected cases; 2) educating the public and medical providers about Zika virus risks, transmission, and prevention strategies, particularly in areas with large populations of immigrants from areas with ongoing Zika virus transmission; 3) monitoring pregnant women with Zika virus infection and their fetuses and infants; 4) detecting local mosquito-borne transmission through both human and mosquito surveillance; and 5) modifying existing Culex mosquito control measures by targeting Aedes species of mosquitoes through the use of larvicides and adulticides.