Diabetic macular edema (DME) is the most common cause of vision loss in diabetic patients. Application of laser photocoagulation has a limited effect. Antivascular endothelial growth factor (anti-VEGF) therapy has been a major breakthrough in the management of DME. Despite the improvement in DME after laser or anti VEGF therapy, persistent type remains a challenge due to different pathogenesis and biochemical pathways. This talk focuses on therapeutic options for resistant (refractory) DME, which include corticosteroids, laser, surgery and new agents.