Radiation pneumopathy is the reaction of the organ lung to radiation effects in various target cells. It starts as an exudative inflammation, with the clinical picture of interstitial pneumonia 6-12 weeks after irradiation, and proceeds to a productive chronic inflammation lasting several months and terminating, as other chronic inflammations do, in scar formation, called lung fibrosis. Lung fibrosis is the common end point after lung damage from a wide range of damaging agents. The pathogenetic process leading to the signs and symptoms of radiation pneumopathy is an integrated response of the complex organization of lung tissue. Clinical and pathologic data in patients do not support the hypothesis that the early inflammatory phase of radiation "pneumonitis" and late "radiation fibrosis" are independent pathogenetic processes in the same way as acute radiodermatitis and subcutaneous fibrosis are separate pathologic entities. The target cell population that initiates the pathogenetic process in the lung is not known, and it has been suggested that no single identifiable target exists. The entire process is the result of complex functional alterations in endothelial cells, pneumocytes, macrophages, and other resident and transient cells. No evidence has been found for a role of stem cell sterilization, for impaired transit cell proliferation, or for hypoplasia, which is the hallmark of other acute inflammatory normal tissue damage (i.e., in the mucosa). The radiobiologic concepts developed in cellular radiobiology are not adequate for the quantitative analysis of radiation pneumopathy. A new analytical framework based on structurally defined intercellular interaction by signaling molecules and their activation needs to be developed. This would not be only an abstract radiobiologic paradigm but would be the key to the development of potential therapeutic interventions in irradiated patients.