Radiation therapy is a critical treatment modality in the management of patients with gynecologic tumors. New highly conformal external-beam and brachytherapy techniques have led to important reductions in recurrence and patient morbidity and mortality. However, patients who receive pelvic radiation for gynecologic malignancies may experience a unique constellation of toxicity because of the anatomic locations, combination with concurrent chemotherapy and/or surgery, as well as potential surgical interventions. Although side effects are often categorized into acute versus late toxicities, several late toxicities represent continuation and evolution of the same pathologic process. Comorbidities and radiation dose can significantly increase the risk of morbidity. Current understanding of the incidence of various morbidities in patients treated with current radiation techniques for gynecologic malignancies, the impact of chemotherapy and surgery, treatment options for those effects, and future areas of research are highlighted. Cancer 2014;120:3870–3883. © 2014 American Cancer Society.