Radiation therapy, either alone or in combination with other types of treatment, is responsible for 40% of cancer cures and 70% of all cancer patients receive radiation therapy at some point during the course of their disease. Radiation therapy has profound effects, both acute and long-term, on skin and connective tissues. Radiation therapy also affects the time course and end result of wound healing, and the risk of postoperative complications. For example, radiation therapy of tumors in the abdomen or in the abdominal wall inevitably affects the integrity of abdominal wall structures and may adversely affect the outcome of operations on the abdominal wall, for example hernia surgery. All surgeons will encounter patients who have undergone or will receive radiation therapy. In these situations, it is important to carefully consider the optimum timing of surgery relative to radiation therapy, to decide which perioperative precautions are needed to minimize the risk of complications, to estimate and inform the patient about the increased risk of complications, and, if surgery is done before a planned course of radiation therapy, to consider how soon after surgery it is safe to commence the radiation treatment. This review will (1) describe features of acute and long term radiation-induced changes in skin and connective tissues; (2) provide a brief overview of the biological mechanisms underlying these changes; and (3) discuss practical considerations that have direct relevance to surgical decision making and postoperative outcome.