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The goal of this review is to update ophthalmologists and orbital and adnexal specialists with the emerging role of targeted monoclonal antibody therapy and radioimmunotherapy for orbital and adnexal non-Hodgkin's lymphoma and other lymphoproliferative disorders of the orbit.Rituximab as monotherapy for indolent lymphoma of the orbit and conjunctiva may be associated with good initial response, but the risk of distant relapse is about 50%. Rituximab may be used in combination with conventional chemotherapy, and such combination therapy may be associated with a higher durable response rate and improved progression-free survival compared with chemotherapy alone. Radioimmunotherapy using targeted monoclonal antibodies with radioactive conjugates is also associated with a more durable response rate than monotherapy with rituximab alone and may be an alternative for treatment of ocular adnexal lymphoma. Radioimmunoconjugates are associated with transient pancytopenia during the first 3 months after treatment. Rituximab monotherapy may be considered as an alternative to systemic steroids for treatment of orbital benign lymphoid hyperplasia.Targeted monoclonal antibody therapy is an intriguing new modality for treatment of orbital, eyelid, or conjunctival lymphoma and can be used in combination with radioimmunotherapy or standard chemotherapy for a more durable response.