Although combination chemotherapy can induce complete remission in a large proportion of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL), 30%-50% of patients will relapse. Gemcitabine has shown promising activity in heavily pretreated patients with HD and NHL even in those who have progressed after autologous stem cell transplantation. Its favorable toxicity profile allows development of combination regimens with other cytotoxic drugs and anti-CD20-targeted therapy, although hematologic toxicities appear to be greater than when gemcitabine is used as a single agent. Prolonged infusion of gemcitabine at a pharmacologically guided dose rate of 10 mg/m2/minute has demonstrated a pharmacokinetic and pharmacodynamic advantage although clinical efficacy of prolonged infusion needs to be established. Thus far, gemcitabine has been mainly tested in relapsed or refractory patients, and its inclusion in front-line therapy may bring about greater benefit. However, as gemcitabine has not been evaluated in randomized studies either alone or in combination with other chemotherapy drugs, its exact role in the treatment paradigm of lymphoma remains to be determined.