Proliferative diabetic retinopathy (PDR) remains a leading cause of blindness in working age individuals in developed countries. Although tight control of both blood sugar and blood pressure are essential in preventing PDR, laser photocoagulation remains the primary treatment. However, laser photocoagulation is a late, destructive intervention that does not specifically address the underlying etiology of diabetic retinopathy (DR). Therefore, new pharmacological treatments based on the understanding of the pathophysiological mechanisms of DR are required. Growth factors and, in particular, vascular endothelial growth factor (VEGF) play a key role in the development of PDR. Hypoxia, hyperglycemia, advanced glycation end-products, proinflammatory cytokines and several growth factors upregulate VEGF expression. Intraocular delivery of anti-VEGF therapies is now widely used to treat age-related macular degeneration, and is currently undergoing evaluation in clinical trials for the treatment of DR. Other grow th factors involved in the pathogenesis of DR are insulin-like growth factor-1, platelet-derived growth factor, basic fibroblast growth factor, hepatocyte growth factor, angiopoietins, connective tissue growth factor and stromal cell-derived factor-1. Increasing the knowledge of the molecular mechanisms involved in their regulation will permit us to develop new therapeutic strategies addressed to ease the burden of this devastating disease. © 2010 S. Karger AG, Basel.