Historically, floods and tsunamis have caused relatively few severe injuries; an exception to that tendency followed the great Andaman Island-Sumatra earthquake and tsunami of 2004. More than 280,000 people died, the coastal plains were massively scoured, and more than 1 million individuals were made homeless by the quake and resulting tsunami, which affected a 10-nation region around the Indian Ocean. This destruction overwhelmed local resources and called forth an unprecedented, prolonged, international response. The USNS Mercy deployed on a unique mission and rendered service to the people and government of Indonesia. This introduction provides background on the nature and extent of the damage, conditions upon arrival of the hospital ship 5 weeks after the initial destruction, and the configuration of professionals aboard (officers and sailors of the U.S. Navy, civilian volunteers from Project HOPE, officers of the U.S. Public Health Service, and officers and civilian mariners of the Military Sealift Command). Constraints on the mission provide context for the other articles of this issue that document and comment on the activities, challenges, methods, and accomplishments of this unique mission's "team of teams," performing humanitarian assistance and disaster relief in the Pacific theater.