In advanced follicular lymphoma, rituximab is currently used with chemotherapy as induction therapy, and as maintenance monotherapy following induction in previously untreated patients and treatment-experienced relapsed/refractory patients. Herein, the authors characterize the clinical effectiveness, safety and cost-effectiveness of rituximab in follicular lymphoma, based on the literature review. Rituximab has a favorable safety profile and has been shown to improve progression-free survival, with some evidence of improvements to overall survival, particularly for relapsed/refractory patients. Rituximab has consistently been found to have a favorable economic profile, with cost per quality-adjusted life year falling within standard thresholds for cost-effectiveness. Challenges in cost-effectiveness analysis include the fact that life expectancy for patients with follicular lymphoma exceeds the period of available follow-up data and that treatment pathways are more complex than the model structures frequently used in oncology models. As data accrue and more complex models are developed, the cost-effectiveness of rituximab can be more accurately assessed.