Diabetes is rapidly increasing in frequency with an attendant toll of complications, including diabetic retinopathy. Although the underlying mechanisms remain elusive, genetic susceptibility is key to both types 1 and 2 diabetes and is increasingly recognized for its contribution to diabetic complications. In this article we review the evidence connecting genetic susceptibility to diabetic retinopathy. Elucidating the susceptibility genes and pathways should permit strategies to slow and reverse the troubling trends for the population, families, and individuals.