A Mega Mass-Casualty Event (MMCE) is a unique and exceptional event, that results in a very large number of casualties (500–5000) needing emergency care in the prehospital and hospital settings. This type of event usually goes beyond the capabilities of a certain region and requires reinforcement of resources from adjacent and remote regions. Due to its exceptional nature, a MMCE dictates a different organization of all emergency services and agencies involved. As a result of the recent experience, and in order to adequately prepare for such future events, a novel MMCE doctrine was developed by a committee of diverse emergency professionals. This doctrine was transferred to guidelines referring to MMCE recognition and the following series of actions that need to taken at all levels. It holds organizational, operational, and clinical aspects, as well as command and control elements. In November 2009, a large-scale drill of 1,000 mock casualties was performed in order to validate and evaluate the MMCE plan. This drill emphasized the need for the involvement of all pertinent emergency services and agencies, and their optimal collaboration and coordination, subjected to regional and national headquarters' command and control. In addition, the need for dedicated educational programs and o-going training was recognized. It was accepted that adequate planning is obligatory for better outcomes in the future.