Diabetic retinopathy (DR) is a sight-threatening chronic complication of diabetes mellitus and is the leading cause of acquired blindness in adults. Long-term exposure to the hyperglycemia of diabetes patients leads to the development of DR. Several studies have provided evidence that good diabetes control is important to prevent DR. However, emerging evidence suggests that genes are a significant contributor to an individual's risk of retinopathy. This evidence is from evalu- ations of familial aggregation and different incidence of DR in racial and ethnic groups. Some groups of patients develop DR despite good control and some escape retinopathy despite poor control. This suggests that the genes are involved in the susceptibility to DR. Genes suggested as having a role include those encoding aldose reductase, nitric oxide synthase, receptor for advanced glycation end products, angiotensin converting enzyme, vascular endothelial growth factors and pigment epithelium-derived factor. An understanding of the role of susceptibility genes will ultimately allow the development of novel therapeutic strategies. This article reviews the role of genetic factors in the etiology and progression of DR.