How to incorporate anti-CD20 monoclonal antibody into frontline treatment for patients with CLL. *All eligible patients should be considered for participation in clinical trials if available. **Anti-C20 monoclonal antibody. ⁺Pending Food and Drug Administration approval for marketing for CLL at time of submission. GERD, gastroesophageal reflux disease; IGHV, immunoglobulin variable heavy chain; TLS, tumor lysis syndrome.