The t(14;18)-translocation can be detected by PCR analysis in more than 90% of cytogenetically t(14;18)-positive follicular lymphomas (FLs), thus providing an easily accessible marker for molecular disease monitoring. Various technical aspects of the detection of residual lymphoma cells as well as the prognostic and clinical significance of the detection of minimal residual disease (MRD) after radiotherapy, chemotherapy and therapy with the monoclonal antibody rituximab are discussed. Up to now the comparability of the different studies investigating minimal residual disease in follicular lymphoma patients is hampered by the use of a variety of PCR techniques. A more standardized quantitative approach based on the real-time PCR technique will provide a powerful tool for the evaluation and optimization of therapy for each individual patient.