Although response rates are increased, the addition of rituximab to induction chemotherapy has not yet been proven to extend the progression-free and overall survival benefits of chemotherapy alone. In first remission, high-dose therapy plus stem cell rescue improves time to treatment failure and progression-free survival when compared with maintenance interferon alpha. However, relapse rate does not reach a plateau. Radioimmunotherapy has substantial single-agent activity and when combined with chemotherapy may provide a platform onto which rituximab or autologous stem cell transplantation can be added. Targeted therapies are also showing promise and may have a role in maintenance and/or initial therapy.