Regulations usually distinguish between prescription‐only (POM) and over‐the‐counter (OTC) medicines. The former requires medical prescription; the latter are available for SM of common minor or easily treated ailments. However, in the Eastern Mediterranean countries, theoretical prescription medicines can easily be purchased without a prescription, as self‐medication (SM) resulting in potential misuse and unnecessary risk for patients. The magnitude of this activity is uncertain. The aim of this article, therefore, is to undertake a comprehensive review to identify the different types of medicines that can easily be purchased as SM in Middle East and recognized as misused. An extensive review of the published literature (1990–2015) was conducted using Pubmed, web of science, Cochrane, and Google Scholar databases, for OTC medicine misuse in the Middle East. A total of 72 papers were identified. Medicines involved in misuse included: codeine containing products, topical anesthetics, topical corticosteroids, antimalarial, and antibiotics. Self‐medication misuse of medicines seemed widespread. Individual treatment patterns were not clearly identified. Studies were not standardized, limiting the comparability between studies and the estimation of the scale of misuse. Pharmacists, friends, or parents were found to be the main sources of SMs. Knowledge and attitudes are an important contributing factor in the misuse of these medications. Strategies and interventions to limit misuse were rarely identified in literature. In conclusion, a massive problem involving a range of medicines was found in Middle East. Standardization of studies is a prerequisite to the understanding and prevention of misuse of self‐medication.