To provide an overview of the current clinical management of retinoblastoma by discussing the trends in the categorization, treatment, and recent advances in molecular diagnostics as well as therapy for retinoblastoma.

Literature review and commentary.

Selected articles from the medical literature and the authors' clinical and research experience were reviewed critically.

Retinoblastoma has evolved from a deadly childhood cancer to a largely curable cancer within the past 40 years. Current treatment strategies aim to salvage the eye and provide the best visual outcome possible. Using the international classification system to stratify intraocular retinoblastoma into treatment groups, the multicenter Children's Oncology Group treatment protocols use 2- to 3-drug chemoreduction with focal consolidative therapy for most categories of disease. Furthermore, collaborative efforts are being directed toward a better understanding of genotype–phenotype relationships in retinoblastoma that will be useful in the multidisciplinary management of this disease. Molecular targeting therapy is emerging as a potential strategy to individualize therapy. Finally, improvements in local drug delivery methods and vehicles are providing solutions for the problem of systemic toxicity from existing chemotherapy regimens.

The management of retinoblastoma has become a prototype for other ophthalmic diseases and systemic cancers in which genetic information and molecular targets are being used to design more elegant treatment strategies.