Diabetic retinopathy (DR) is one of the leading causes of preventable blindness worldwide. It is characterized by a spectrum of disease that spans mild non-proliferative diabetic retinopathy (NPDR) all the way to neovascular glaucoma and tractional retinal detachment secondary to proliferative diabetic retinopathy (PDR). Most eyes with DR remain asymptomatic unless vision-threatening complications, such as diabetic macular edema (DME) and/or PDR, develop. Current treatment options include laser photocoagulation and/or anti-VEGF intravitreal injections. Patients under treatment with anti-VEGF agents usually require constant monitoring and multiple injections to optimize outcomes. This treatment burden plays a key role in suboptimal adherence to treatment in many patients, compromising their outcomes. Gene therapy has emerged as a promising therapeutic option for DR. The mechanism for current trials evaluating gene therapies for DR consists of delivering transgenes to the retina that express anti-angiogenic proteins that inhibit VEGF. Preliminary results from the SPECTRA (4D-150) and ALTITUDE (ABBV-RGX-314) studies are promising, demonstrating an improvement in the diabetic retinopathy severity score and a reduction in the treatment burden. In contrast, the INFINITY (ADVM-022) trial was complicated by several cases of severe inflammation and hypotony that led the sponsor to discontinue further development of this product for DME.