We review current literature and data on the burden of injury and violence in the Eastern Mediterranean Region (EMR) of the World Health Organization (WHO), with a special focus on the health, economic and social burden they impose on individuals, families and society. Injury-associated mortality and disability is on the rise in EMR, especially among economically productive adults, young males and vulnerable road users. In particular, road traffic injuries, the leading cause of injuries, account for 27% of the total injury and violence mortality in EMR according to WHO. Violence including suicide, homicide and war-related injury has also been increasing over the past two decades for both females and males. There is need for greater interest and efforts in slowing and ultimately halting the trend through interventions, legislative actions, and research that examine the special needs and challenges in the Region.