Diabetic retinopathy is one of the major complications of diabetes mellitus and a leading cause of visual loss. Diabetic macular edema (DME) is an ocular manifestation of the disease causing visual deterioration. The prevalence of visual impairment due to DME is estimated to be 5.4% in Europe. Vascular endothelial growth factor (VEGF) is overexpressed in diabetic eyes and plays a key role in the development of DME. VEGF levels were proven to be elevated in the vitreous and retina in patients with diabetic retinopathy. VEGF causes a breakdown of the blood-retinal barrier by influencing the tight junctions of retinal endothelial cells and leading to accumulation of fluid in the macula. Therefore, intravitreal VEGF inhibitors are ideal candidates to treat DME by counteracting VEGF overexpression. This review summarizes the results of the most recent prospective, controlled studies on DME with promising novel VEGF inhibitors. It focuses on the efficacy and safety aspects of anti-VEGF treatment of DME.