Proliferative diabetic retinopathy (PDR) demands both more effective and less expensive biologically based treatments. Our understanding of the pathophysiology of the disease is increasing as new biochemical pathways are identified. Most reports emphasize proangiogenic stimuli, with the natural inhibitory elements receiving little attention. There are two therapeutic strategies for blocking retinal angiogenesis in PDR: systemic drug administration (protein kinase C inhibitors and somatostatin analogs) or local therapies (anti-vascular endothelial growth factor strategies, anti-inflammatory agents, gene therapy and stem cell therapy). This review mainly focuses on the role of local therapies, especially intravitreous delivery, in the management of PDR. The potential for adverse effect are also discussed. The availability of these new strategies or the combination of them will not only be beneficial in treating PDR but may also result in a shift towards treating earlier stages of diabetic retinopathy, thus easing the burden of this devastating disease.