The optimal timing and technique of breast reconstruction in patients who may require postmastectomy radiation therapy are controversial. To help surgeons make the best decisions, the authors reviewed the recent literature on this topic. The authors searched the MEDLINE database for studies of radiation therapy and breast reconstruction with most patients treated after 1985 and mean follow-up of more than 1 year. Forty-nine articles were reviewed. Even with the latest prosthetic materials and modern radiation delivery techniques, the complication rate for implant-based breast reconstruction in patients undergoing postmastectomy radiation therapy is greater than 40 percent, and the extrusion rate is 15 percent. Modified sequencing of two-stage implant reconstruction, such that the expander is exchanged for the permanent implant before postmastectomy radiation therapy, results in higher rates of capsular contracture and is not generally feasible after neoadjuvant chemotherapy. Current evidence suggests that postmastectomy radiation therapy also adversely affects autologous tissue reconstruction. Even with modern radiation delivery techniques, immediate implant-based or autologous tissue breast reconstruction can distort the chest wall and limit the ability to treat the targeted tissues without excessive exposure of the heart and lungs. In patients for whom postmastectomy radiation therapy appears likely but may not be required, "delayed-immediate reconstruction," in which tissue expanders are placed at mastectomy, avoids the difficulties associated with radiation delivery after immediate reconstruction and preserves the opportunity for the aesthetic benefits of skin-sparing mastectomy. In patients who will receive or have already received postmastectomy radiation therapy, the optimal approach is delayed autologous tissue reconstruction after postmastectomy radiation therapy. If postmastectomy radiation therapy appears likely but may not be required, delayed-immediate reconstruction may be considered.