Follicular lymphoma (FL) is typically characterized by repeated remissions and relapses, and many patients receive a therapeutic interventions during their disease course. Although treatment options are evolving rapidly, stem cell transplantation a potentially favorable impact on survival. In general, many patients with FL are not eligible for this approach by virtue of age comorbid disease. Salvage chemotherapy consequently remains the mainstay of treatment, being individualized according to disease patient characteristics, goals of therapy, and patient preference. Many of the cytotoxic agents used in relapsed FL are highly leading to significant morbidity and mortality, including febrile neutropenia, hemorrhage, and impaired quality of life. Nausea and can also be problematic, particularly with regimens incorporating carmustine, cisplatin, and high-dose cyclophosphamide. Other toxicities include mucositis, alopecia, extravasation injuries, and neurotoxicity. Late toxicities can also occur, sometimes months or years after the administration of antineoplastic agents. Acute myeloid leukemias, myelodysplastic syndromes, or solid tumors can after chemotherapy with alkylating agents. The cardiotoxic profile of anthracycline antibiotics is well recognized, and several including carmustine and cyclophosphamide, can cause lung injury. Persistent neurotoxicity, nephrotoxicity, ototoxicity, and toxicity have also been reported in association with chemotherapeutic agents used in patients with relapsed FL. Novel strategies might allow patients to achieve longer remissions, potentially reducing lifetime exposure to repeated cycles of and their attendant toxicities. These could include the use of more efficient preparative and purging approaches in the setting or the administration of rituximab maintenance therapy after (immuno) chemotherapy induction or transplantation.