Vitreoretinal lymphoma is the most common type of intraocular lymphoma. It is mostly a high-grade B-cell malignancy with a poor prognosis, and is often associated with primary central nervous system lymphoma. Since intraocular lymphoma was first recognized almost 60 years ago, its treatment has gradually evolved. In the early years enucleation was often performed. Since that time, radiation therapy alone, systemic chemotherapy alone, or a combination of the two have been used extensively Because of the limited intraocular penetration of drugs administered systemically, the systemic and local toxicity of chemotherapy and radiation therapy and the high rate of recurrence, intravitreous chemotherapy, mainly using methotrexate, has become popular in the last decade, with encouraging results. More recently, biological treatment with intravitreal injections of rituximab has been investigated, with good results and minimal side effects. This review summarizes the present knowledge on vitreoretinal lymphoma therapy, with an eye to future molecular approaches.