Diabetic macular edema (DME), defined as a retinal thickening involving or approaching the center of the macula, represents the most common cause of vision loss in patients affected by diabetes mellitus. In the last few years, many diagnostic tools have proven to be useful in the detection and the monitoring of the features characterizing DME. On the other hand, several therapeutic approaches can now be proposed on the basis of the DME-specific characteristics. The aim of the present chapter is to thoroughly delineate the clinical and morphofunctional characteristics of DME and its current treatment perspectives. The pathogenesis and the course of DME require a complex approach with multidisciplinary intervention both at the systemic and local levels.