Khat use is a drug problem characteristic of the Eastern Mediterranean Region, which is a widespread culturally accepted practice in some countries and is becoming more prevalent in others. Although limited use may not be accompanied by serious consequences, prolonged exposure could lead to dependence, psychosis and other psychiatric disorders and physical conditions such as hypertension, cardiovascular complications, sexual dysfunction, hepatoxicity and reduced birth weight of infants born to khat-chewing mothers. The widespread use and its burden on health and economy has raised concerns in the Region, although the extent of the problem is not well assessed. Additionally, most countries do not have a clear policy and plan with regard to khat use, and therefore there is hardly any structured prevention and treatment plan in place to respond to the problem. This review presents a picture of the extent of the problem, elaborates on related existing research initiatives and international treaties, policies and health service provisions, and outlines best policy and programme interventions in khat-use countries.