With major depressive disorder (MDD) associated with significant clinical, economic and health-related quality of life impact, we sought to systematically review and synthesize information relevant to the burden of MDD in Africa and the Middle East, from which published evidence is slim. Our literature search identified 54 publications assessing epidemiological (43), humanistic (5), clinical/treatment (7) or economic outcomes (2). General population MDD prevalence and that among chronic disease populations were similar in Africa and the Middle East. No MDD-related economic literature specific to Africa or the Middle East was identified. Five studies of humanistic outcomes were identified; four African studies documented significant reduction of health-related quality of life related to MDD. The frequency of certain risk factors for MDD, such as disease, trauma and associated stress, as well as patterns of MDD treatment, suggest the potential for a higher burden of disease in Africa and the Middle East than in western countries.