The explosion on the Deepwater Horizon disaster oil rig on April 20, 2010 resulted in the death of 11 workers and injury to another 17 workers. In the weeks and months after, as large amounts of crude oil released from the Macondo Well, tens of thousands of workers engaged in on- and off-shore containment and clean-up activities. Addressing concerns about the potential effects of the spill on human and environmental health in the Gulf, including potential risk to response workers, prompted an unprecedented response from agencies all across the Federal government. On May 3, 2010, experts from the National Institute for Occupational Safety and Health (NIOSH) arrived on site at the Gulf of Mexico. The role NIOSH had in this interagency effort was to anticipate and address the occupational safety and health needs of the containment and cleanup response workers in close collaboration with the Occupational Safety and Health Administration (OSHA). As part of these activities, NIOSH led efforts in rostering workers, conducting health hazard evaluations, providing technical guidance by means of a joint OSHA/NIOSH publication, conducting health surveillance activities, and performing toxicity testing. The Deepwater Horizon Response (DWHR) effort presented unique challenges in protecting response workers spread across the Gulf region, who performed a wide range of activities in physically and emotionally demanding circumstances. The DWHR presented opportunities to further expand our knowledge and understanding of protecting workers in complex, large-scale emergency responses. With the publication of "Lessons Learned from the Deepwater Horizon Response," NIOSH hopes to share the knowledge gained during this response (including the application of knowledge gained from past large-scale emergency responses), report how we can improve our response to similar events in the future, and facilitate a dialogue between NIOSH and partners in the government, industry, labor and academia on ways to improve the overall response to both natural and man-made disasters.