Standard first line treatment for advanced FL consists of alkylating-based (CVP) or anthracycline containing regimen in association to interferon alpha (CHVP+IFN) chemotherapy. Others approaches have been developed mostly as secondary therapy including purine analogs alone or in combination with alkylators or mitoxantrone, high dose therapy with autologous peripheral stem cell transplantation and, more recently, treatment with the unconjugated chimeric anti-CD20 antibody (rituximab) to target the CD20 antigen highly expressed on follicular lymphoma cells. None of these strategies does appear to give a definitive survival advantage. Thus, in patients with FL, the design of novel combination programs is a major challenge.