Glucose-6-phosphate dehydrogenase (G6PD) Deficiency is the most prevalent enzymopathy in mankind. It has sex-linked in­heritance. This enzyme exists in all cells. G6PD deficiency increases the sensitivity of red blood cells to oxidative dam­age. G6PD deficiency was discovered in 1950 when some people suffered hemolytic anemia as a result of taking antimalar­ial drugs (primaquin). Most people with G6PD deficiency do not have any symptoms, till they are exposed to certain medi­cations, Fava beans and infections; and then their red blood cells are hemolyzed. The degree of hemolysis changes accord­ing to the degree of enzyme deficiency and the oxidant agent exposure. G6PD deficiency has many different variants and Medi­terranean variant is the most common mutation in the world. G6PD deficiency is considered a health problem world­wide, especially in Asia, Middle East and Mediterranean countries. In this article, we have reviewed the importance and func­tion of G6PD enzyme, incidence rate of G6PD deficiency in the world and Iran, genetic and variants of this enzyme, clini­cal manifestation, diagnosis and treatment of the enzyme deficiency.