OBJECTIVES: An orphan drug is a drug developed specifically to treat a rare medical condition. It is unclear how well rare-disease patients in the Middle East are able to obtain orphan drugs. In this study,  we provide a critical review of the literature on the availability of orphan drugs in the Middle East. METHODS: Using Medline and other internet-based search engines, a critical review of both English and Arabic literature and other documents was performed to identify and evaluate 1) the prevalence of rare diseases in the Middle East; 2) problems with diagnosis of rare diseases in Arab countries; 3) availability of orphan drugs in the Middle East; and 4) development by pharmaceutical companies of orphan drugs for Arab diseases. RESULTS: Approximately 2.8 million patients are estimated to be suffering from a rare disease in the Middle East. Genetic disorders such as haemoglobinopathies, glucose-6-phosphate dehydrogenase deficiency, and autosomal recessive syndromes have a presence throughout the Middle East, with the latter’s occurring in approximately 1 out of 3,500 newborns.  The prevalence of Behcet disease was estimated to be 2.23, 1.35, and 1.25 per 100,000 in Bahrain, Kuwait, and Oman, respectively. To help with diagnosis, the Centre for Arab Genomic Studies has constructed a rare-disease database. Despite the high expense of orphan drugs, some health care companies, such as Taiba, currently market and distribute orphan drugs.  The Dubai Biotechnology & Research Park provides an environment for life sciences companies to work in the Middle East. CONCLUSIONS: In order to promote the treatment of rare diseases, Middle Eastern governments need to facilitate education and training of health care personnel; develop and execute a method for obtaining and paying for orphan drugs; and provide tax, marketing, and other incentives to domestic and international firms to develop drugs specifically for the diseases of most importance to Middle Eastern patients.