Management of retinoblastoma has evolved drastically with the advent of targeted chemotherapy, such as intra-arterial chemotherapy, intravitreal chemotherapy, and intracameral chemotherapy. Intravitreal chemotherapy has emerged as the frontline therapy for the management of vitreous seeding. It has also shown beneficial effects on subretinal seeding, the 2 major therapeutic challenges for globe salvage in retinoblastoma. The enhanced efficacy and safety of current intravitreal agents have led to improved globe and vision salvage, resulting in better survival outcomes. The authors discuss current trends, indications, and practice patterns of intravitreal chemotherapy for retinoblastoma, highlighting potential groundbreaking advancements, including the role of nanoparticle technology.