Diabetic macular edema (DME) is the leading cause of blindness in patients with diabetic retinopathy worldwide. Therapeutic alternatives now include focal/grid laser photocoagulation, vitreoretinal surgery, and intraocular injection of anti-angiogenic and steroid molecules. In patients with recalcitrant DME, especially in those cases when anti-vascular endothelial growth factor (VEGF) agents are contraindicated or a treatment regimen with fewer intravitreal injections is required, intravitreal administration of steroids represents a fundamental alternative. Three intravitreal corticosteroid options for DME treatment are currently available including the dexamethasone delivery system, the fluocinolone acetonide insert, and off-label intravitreal triamcinolone acetonide. All of these drugs are associated with the risk of cataract progression and intraocular pressure elevation. In patients unresponsive to anti-VEGF therapy, pseudophakic, at low risk for glaucoma, or who have significant cardiovascular risk, treatment with long-lasting intraocular steroids is suggested.