Radiotherapy-induced lung toxicity might compromise the success of current efforts regarding lung cancer treatment intensification. Compounds which prevent lung toxicity without affecting the radiosensitivity of the tumor can contribute to improvement of cure rates. Basic research on radiotherapy-induced lung reactions significantly improved our understanding of the molecular and cellular mechanisms underlying acute radiation pneumonitis and the tissue remodelling leading to lung fibrosis. Identification of mediators such as various adhesion molecules, cytokines and growth factors in this process allows for innovative intervention studies. This review summarizes translational research data as well as clinical strategies for response modification and prediction.