Diabetic macular edema is a major cause of visual impairment. The pathogenesis of macular edema appears to be multifactorial. Laser photocoagulation is the standard of care for macular edema. However, there are cases that are not responsive to laser therapy. Several therapeutic options have been proposed for the treatment of this condition. In this review we discuss several factors and mechanisms implicated in the etiology of macular edema (vasoactive factors, biochemical pathways, anatomical abnormalities). It seems that combined pharmacologic and surgical therapy may be the best approach for the management of macular edema in diabetic patients.