Skin changes caused by ionizing radiation have been scientifically documented since 1902. Ionizing radiation is a widely accepted form of treatment for various types of cancer. Despite the technological advances, radiation skin injury remains a significant problem. This injury, often referred to as radiation dermatitis, occurs in about 95% of patients receiving radiation therapy for cancer, and ranges in severity from mild erythema to moist desquamation and ulceration. Ionizing radiation is not only a concern for cancer patients, but also a public health concern because of the potential for and reality of a nuclear and/or radiological event. Recently, the United States has increased efforts to develop medical countermeasures to protect against radiation toxicities from acts of bioterrorism, as well as cancer treatment. Management of radiation dermatitis would improve the therapeutic benefit of radiation therapy for cancer and potentially the mortality expected in any "dirty bomb" attack. Currently, there is no effective treatment to prevent or mitigate radiation skin injury. This review summarizes "the good, the bad, and the ugly" of current and evolving knowledge regarding mechanisms of and treatments for radiation skin injury.