The human/mouse chimeric monoclonal antibody rituximab has been used extensively in treatment of hematologic malignancies, and its efficacy and safety are well established, both as single-agent therapy and when used in combination with chemotherapy. Mild-to-moderate, transient infusion-related reactions are the most common adverse event, and rituximab does not add significantly to the toxicity of chemotherapy. Rituximab maintenance therapy has now emerged as an effective treatment for follicular lymphoma. Patients on rituximab maintenance therapy receive regular doses of rituximab for periods up to 2 years after initial induction therapy and are completely depleted of B-cells throughout this time, although B-cells eventually recover when maintenance treatment is stopped. In randomized trials of rituximab maintenance therapy versus observation after induction with single-agent rituximab, standard chemotherapy or rituximab plus chemotherapy, patients receiving rituximab maintenance therapy did not experience significantly greater toxicity than those in the observation arms, and no cumulative or unexpected toxicities were observed. Findings to date thus indicate that rituximab maintenance therapy is well tolerated, but further assessment of the long-term effects of prolonged B-cell depletion is still required.