Background and Purpose: The aim of the present paper is to update the practical guidelines for radiotherapy of breast cancer published in 2006 by the breast cancer expert panel of the German Society for Radiooncology (DEGRO). These recommendations were complementing the S3 guidelines of the German Cancer Society (DKG) elaborated in 2004. The present DEGRO recommendations are based on a revision of the DKG guidelines provided by an interdisciplinary panel and published in February 2008. Methods: The DEGRO expert panel (authors of the present manuscript) performed a comprehensive survey of the literature. Data from lately published meta-analyses, recent randomized trials and guidelines of international breast cancer societies, yielding new aspects compared to 2006, provided the basis for defining recommendations referring to the criteria of evidence-based medicine. In addition to the more general statements of the DKG, this paper emphasizes specific radiooncologic issues relating to radiotherapy after mastectomy (PMRT), locally advanced disease, irradiation of the lymphatic pathways, and sequencing of local and systemic treatment. Technique, targeting, and dose are described in detail. Results: PMRT significantly reduces local recurrence rates in patients with T3/T4 tumors and/or positive axillary lymph nodes (12.9% with and 40.6% without PMRT in patients with four or more positive nodes). The more local control is improved, the more substantially it translates into increased survival. In node-positive women the absolute reduction in 15-year breast cancer mortality is 5.4%. Data referring to the benefit of lymphatic irradiation are conflicting. However, radiotherapy of the supraclavicular area is recommended when four or more nodes are positive and otherwise considered individually. Evidence concerning timing and sequencing of local and systemic treatment is sparse; therefore, treatment decisions should depend on the dominating risk of recurrence. Conclusion: There is common consensus that PMRT is mandatory for patients with T3/T4 tumors and/or four or more positive axillary nodes and should be considered for patients with one to three involved nodes. Irradiation of the lymphatic pathways and the optimal time point for onset of radiotherapy are still under debate.