Retinoblastoma with vitreous seeding has been one of the most challenging conditions for eye-preservation therapy. Several modalities for treating vitreous seeding were reviewed in order to analyze the problems associated with them. External beam radiotherapy has been the most reliable method to treat vitreous seeding. However, recurrence after external beam radiotherapy needs other types of treatments to preserve the eyeballs. Due to the progress of investigations concerning retinoblastoma, chemotherapy has become the most promising method to cure not only recurrence but also primary tumors. Systemic chemotherapy can rarely cure vitreous seeding, but local chemotherapy using vitreous injections of melphalan can preserve about 50% of the eyeballs with vitreous seeding. Currently, animal experiments are being conducted to study the efficacy and safety of vitreous surgery combined with infusion of anticancer drugs for eradication of vitreous seeds and maintenance of visual function.