The combination of high-dose radiotherapy with intensive chemotherapy may improve the prognosis of patients with inoperable, locally advanced non-small-cell lung cancer. In the design of suitable clinical protocols, potential interactions of drugs and radiation in the tumour, the lung and other critical normal tissues have to be considered.From experimental data on chemotherapy radiotherapy interactions and based on knowledge about the biology of non-small cell lung cancer and the pathogenesis of radiation pneumopathy, the principles which should be considered in the design of treatment schedules are developed.For the increase in local tumour control, further escalation of radiation dose should be considered first. The most critical issue for lung toxicity may be the volume of the 30 Gy isodose. Yet, the most critical normal tissue which may limit the further increase in dose and dose intensity appears to be the oesophagus.Since the main cause of treatment failure remains local recurrence, further increase in locoregional cytotoxicity is the first priority in locally advanced non-small-cell lung cancer. This can best be achieved by increasing radiation dose and dose intensity further. Yet, there may also be a role for simultaneous radiochemotherapy, even if this would increase the lung volume which develops radiation pneumopathy and thus the severity of symptoms. This problem should be dealt with by reducing the irradiated lung volume by use of conformal treatment planning. The most critical side effects will then be due to increased severity of acute oesophagitis.