Diabetic macular edema (DME) is the leading cause of vision loss among patients with diabetes. This monograph presents a variety of challenging real-world DME cases. The benefits of glycemic control on the preservation of vision will be highlighted. Precautions regarding antidiabetes medications that may exacerbate DME are also discussed. Evidence-based guidelines are utilized to develop effective DME treatment strategies that include laser, VEGF inhibition, intravitreal steroid delivery devices, and vitreoretinal surgery.