In Brief Purpose: To report globe salvage using chemoreduction (CRD) for advanced retinoblastoma in a glaucomatous eye with buphthalmos. Methods: Case report. Results: A 7-month-old girl presented with epiphora and buphthalmos in the right eye. She was found to have bilateral retinoblastoma. Classified as group E, the right eye exhibited a total retinal detachment and buphthalmos from secondary glaucoma. The left eye was classified as group B. Systemic workup revealed no metastatic disease. CRD was employed with future planned enucleation of the right eye. After six cycles of CRD and focal consolidating treatments, complete regression of retinoblastoma in both eyes was achieved. The right eye showed complete resolution of the retinal detachment and no active tumor or seeds at 18 months follow-up, allowing for salvage of the eye. Conclusion: In this child with secondary glaucoma and buphthalmos from retinoblastoma, CRD provided complete tumor control and globe salvage. A 7-month-old girl with unilateral buphthalmos was found to have bilateral retinoblastoma. Following six cycles of chemoreduction, complete regression of retinoblastoma was achieved, allowing for salvage of the eye with secondary glaucoma and buphthalmos.