Diabetic retinopathy is the most common microvascular complication of diabetes mellitus and is the leading cause of blindness amongst working-age adults in Western countries. Large observational and randomized studies have consistently shown that optimal blood glucose and blood pressure control is the key component of intervention strategies aimed to halt or regress the disease, and limit the risk of progression to the proliferative stage, with consequent visual loss up to blindness in most severe cases. Amelioration of dyslipidemia by statins, especially if combined with fenofibrate, may also ameliorate retinopathy in line with a potential pathogenic role of hyperlipidemia. Recently, evidence has also emerged that renin-angiotensin system (RAS) inhibitors may electively prevent or delay progression of retinopathy, possibly because of specific protective effect against the structural and functional retinal changes sustained by local RAS activation. Thus, metabolic and blood pressure control by RAS inhibition is to prevent or limit the onset of retinopathy and its progression towards visual-threatening stages. Topic treatment with anti-vascular endothelial growth factor (VEGF) agents is emerging as a treatment option for retinopathy in advanced stages to limit the need for laser photocoagulation. This option however should be considered with caution due to the risk of systemic adverse events.