Chemotherapy is the main treatment in many human malignancies including non-Hodgkin lymphomas and some solid tumors such as those of embryonal origin and small cell lung carcinomas. The high responsiveness to chemotherapy of these tumors has led some groups to treatment policies limited to chemotherapy alone. A long follow-up has shown a high incidence of recurrence in the sites that were initially macroscopically involved. Some randomized trials evaluating the adjunction of radiotherapy to chemotherapy have shown that a failure in local control can be associated with a decreased overall survival. The survival benefit of combined chemotherapy and radiotherapy is generally moderate and is best evaluated by randomized trials entering a large number of patients. The adjunction of radiotherapy to chemotherapy can lead to an increased rate of acute and late toxicity that may overshadow a therapeutic benefit. Critical points of the combined approach are: types of drugs, radiotherapy parameters, radiotherapy-chemotherapy doses, and timing. In this review, two clinical models, one with a low potential of cure, limited small cell lung cancer, and one with a medium potential of cure, non-Hodgkin lymphoma, are reviewed emphasizing information obtained from randomized trials. The modalities of combining radiotherapy and chemotherapy, particularly the timing, are analyzed to define optimal schedules for a definite therapeutic gain.