Retinoblastoma is the most common primary intraocular malignancy worldwide. The known established standard therapies for bilateral disease, such as external beam radiation therapy or systemic chemotherapy often lead to a higher morbidity and increased risk of secondary malignancies, especially with radiation therapy. Therefore, new non-systemic chemotherapy strategies, such as the intra-arterial or intravitreal administration of melphalan are being revised with the aim of reducing systemic side effects.