Successful treatment of non-small cell lung cancer requires adequate local and systemic disease control. Although it has been shown to have superior results, high-dose radiation therapy is not a current practice largely because of concerns of normal tissue toxicity. This article reviews and updates the possible mechanism of radiation-induced pneumonitis and fibrosis, their associations with dose intensity, and the role they may play in making treatment decisions. The commonly used clinical terminology and grading systems are summarized. Pneumonitis and fibrosis after 3-dimensional conformal high-dose radiation are reviewed, including recent updates from radiation dose escalation trials. Chemotherapy- and chemoradiation-related lung toxicities are also discussed. Individual susceptibility and potential predictive models are examined; dose and 3-dimensional dosimetric parameters are reviewed along with estimation of normal tissue complication probability and biologic predictive assays. Based on the risk levels of toxicity for each patient, future clinical trials may be designed to maximize individual therapeutic gain.