A novel strain of influenza A virus H1N1 surfaced in Mexico in April 2009 and quickly spread across the globe, turning an epidemic into a pandemic. Within two months, the World Health Organization (WHO) declared an international health emergency and raised the threat bar from level V to level VI, i.e. containment to mitigation. During this time, the WHO Regional Office for the Eastern Mediterranean worked closely with its Member States, other stakeholders and WHO headquarters to manage the situation. This report examines the steps taken as part of this response. Programme documents were reviewed and key personnel interviewed for this study. A hallmark of the response was the establishment of the Strategic Health Operations Centre to bring together experts from different technical backgrounds at regional level. Several lessons were learnt that can provide the basis for standard operating procedures, protocols and guidelines for emergency events in future.