Diabetic macular edema (DME) is a common sight-threatening complication of diabetes caused by inflammatory, vascular, and metabolic processes. Treatment with anti-VEGF agents has fundamentally changed the management of DME and is the mainstay of therapy today. Clinical evidence supports the use of ranibizumab, aflibercept, and conbercept. Additional options include intravitreal corticosteroids and subthreshold micropulse laser therapy. Recent advances include dual-pathway inhibition with faricimab, systemic drugs such as sodium-glucose cotransporter-2 inhibitors, and metformin. New strategies improve treatment durability through long-acting anti-VEGF formulations and gene therapies. These approaches lead to a more permanent and individualized management of DME.