Rituximab is the first and most widely adopted anti-CD20 monoclonal antibody, and has dramatically improved outcomes for patients with B-cell malignancies. Rituximab is active as a single agent and when combined with chemotherapy improves both response rates and survival compared with chemotherapy alone. This approach has become standard of care in this setting. A number of Phase III studies using extended applications of rituximab have demonstrated that patients achieve a significantly longer progression-free survival, at the cost of an increase in infective complications. This has resulted in the widespread adoption of maintenance rituximab following the completion of primary therapy. Rituximab is useful in both previously untreated patients and at relapse, although a subset of patients develop disease that is rituximab resistant, which along with histologic transformation remains a significant management problem for patients with follicular lymphoma. The toxicities are modest and manageable, including infusion reactions, late-onset neutropenia, impaired humoral immunity, reactivation of hepatitis and possibly pulmonary toxicity.