Introduction: Retinal diseases, such as macular edema from diabetic retinopathy and neovascular age-related macular degeneration, are important causes of visual impairment. Pharmacologic intervention has been employed, since laser can have limited success with improving vision. Topical eye drops and systemic therapy deliver low drug levels to the retina and the potential for systemic drug absorption and the accompanying side effects are high. As a result, transscleral and intravitreal drug delivery systems have had increasing importance in treating retinal diseases to deliver therapeutic drug concentrations and to limit the systemic drug exposure. Herein, we will review the novel drug delivery approaches for treating diabetic macular edema and neovascular age-related macular degeneration. Material and Methods: A Medline search was performed to identify articles that described novel drug delivery systems for treating diabetic macular edema and neovascular age-related macular degeneration. Our review was limited to intravitreal drug delivery systems that have recently completed phase II/III clinical trials and/or have been approved by the US Food and Drug Administration. Results: Journal articles were identified from the literature search and reviewed. Conclusions: Local administration of drugs using primarily intravitreal delivery systems is important in treating retinal diseases. Novel drug delivery approaches for treating diabetic macular edema currently are focused on sustained-release corticosteroids. For neovascular age-related macular degeneration, frequent intravitreal injections of anti-vascular endothelial growth factor compounds are the standard of care. Unmet needs in this population are therapies that reduce the treatment burden and improve visual acuity in a greater proportion of patients.