Patients with locally advanced lung cancer (non-small cell lung cancer or small cell lung cancer ) are threatened by concurrent risks of local, regional, and distant failure. By improving locoregional and systemic control within multimodality protocols, the brain emerges as one of the major relapse sites; therefore, prevention of brain relapse has become a primary focus of attention. Prophylactic cranial irradiation (PCI) has a high potential to reduce the risk of brain metastases. Clear evidence exists from meta-analysis that PCI improves overall and disease-free survival rates for patients with SCLC in complete remission. Long-term toxicities, predominantly neurocognitive impairments, represent potential risks, but within large prospective trials, including adequate control groups, late complications of clinical significance rarely have been observed. PCI is the recommended standard of care for the patients with limited disease SCLC in complete remission. As long as the optimal dose and fractionation remain to be defined in this setting, conventional fractionation with moderate total doses of approximately 30 Gy is preferred. In patients with locally advanced stage III non-small cell lung cancer treated within multimodality protocols, comparable relative risks for cumulative brain relapse have been demonstrated in long-term survivors. Although not the standard of care in this situation, the scientific community should be encouraged to further investigate PCI in these patient subgroups within carefully designed clinical trials, including untreated control arms.