The Italian Society of Hematology (SIE) and the two affiliated societies (SIES and GITMO) commissioned a project to develop clinical practice guidelines for the treatment of nodal indolent non-Hodgkin's lymphomas (NHL). Key questions clinically relevant to the management of patients with nodal indolent NHL were formulated by an Advisory Committee and approved by an Expert Panel composed of eight senior hematologists. After a comprehensive, systematic review of the literature, the Expert Panel formulated therapy recommendations and graded them according to the supporting evidence. An explicit approach to consensus methodologies was used for evidence interpretation and for providing recommendations based on poor evidence. The Expert Panel formulated recommendations on when to start a lymphoma-specific therapy, which first-line therapy to choose and which therapy to adopt for patients with relapsed, refractory and transformed disease. Treatment deferral was recommended for patients with stage III-IV disease without systemic symptoms, high tumor burden, extranodal disease, cytopenia due to marrow involvement, leukemic phase, serous effusion and high lactate dehydrogenase levels. Patients with stage I-II disease and a low tumor burden should receive frontline external involved-field radiotherapy, while patients with a high tumor burden or a severe prognostic score should receive front-line chemotherapy plus involved-field radiotherapy. Younger patients with stage III-IV disease should receive front-line therapy with anthracycline- or fludarabine-based regimens combined with rituximab, while older patients who are candidates for treatment should receive single-agent alkylating therapy. By using a systematic literature review and an explicit approach to consensus among experts, recommendations for the key therapeutic decisions in patients with nodal indolent NHL are provided.