Lymphoid malignancies may affect the eye either as primary intraocular lymphomas (PIOL), or by secondary involvement of a nodal lymphoma. PIOL is a subtype of primary central nervous system (CNS) lymphoma and in up to 98% of the cases are non-Hodgkin's B cell lymphomas. PIOL may occur in isolation, without involvement of the CNS. They may affect both the vitreous and the retina, while secondary invasion predominantly affects the uvea. Both forms frequently masquerade as intraocular inflammation or uveitis. Systemic chemotherapy, alone or in combination with radiotherapy has been used in the past for the treatment of PIOL. Methotrexate and rituximab are immunomodulatory agents used in the treatment of cancer and autoimmune diseases. Recent reports have shown the intraocular safety and efficacy of both of these agents for the treatment of PIOL.