Non-Hodgkin's lymphomas are highly sensitive to treatment and complete clinical responses are often achieved. However, disease recurrence is common and is caused by the persistence of malignant lymphoma cells at a level below the limits of detection by conventional assessment such as clinical examination, bone marrow morphology and CT scans. This minimal residual disease can be detected using molecular techniques such as the polymerase chain reaction (PCR), and treatments capable of eliminating minimal residual disease are described as producing molecular remission. Molecular assessment is now commonly used as a measure of outcome in clinical trials of novel therapies for the treatment of lymphoma. The evidence for using molecular remission as a surrogate marker of clinical response in this setting is reviewed and the significance of minimal residual disease in determining prognosis and planning treatment strategies is addressed.