Proliferative diabetic retinopathy (PDR), characterized by pathologic retinal angiogenesis, is a major cause of blindness in the USA and globally. Treatments targeting vascular endothelial growth factor (VEGF) have emerged as a beneficial part of the therapeutic armamentarium for this condition, highlighting the utility of identifying and targeting specific pathogenic molecules. There continues to be active research into the molecular players regulating retinal angiogenesis, including pro-angiogenic factors, anti-angiogenic factors, and integrins and matrix proteinases. New insights have been especially prominent regarding molecules which regulate specialized endothelial cells called tip cells, which play a lead role in endothelial sprouting. Together, these research efforts are uncovering new, important molecular regulators of retinal angiogenesis, which provide fertile areas for therapeutic exploration. This review discusses potential molecular targets, with an emphasis towards newer targets.