Over the past 10 years, improving the outcome of breast cancer patients with brain metastases has become an important challenge. The suboptimal results of whole-brain radiation therapy (WBRT) in these patients have led to the development of irradiation modalities with new technical and biological approaches. By ensuring better sparing of critical organs such as the hippocampus, highly conformal irradiation therapy may partially preserve long-term neurocognitive functions. An additional radiation boost to the tumor bed improves local control. Radiosensitizing agents and radioprotectors that modify response to radiation have also been designed to improve the efficacy of treatment or prevent neurological toxicity. This Review outlines the current strategies and novel developments in WBRT, with a particular focus on new irradiation modalities and experiences of radiosensitization.