This chapter provides an overview of key topics in the area of radiation safety. Three clinical vignettes will serve to frame the review of the literature around both diagnostic radiation exposure and the risk of radioisotope contamination. Advancement in medical technology is rarely innocuous, and the use of radiation as both means to diagnose and treat certain conditions is not an exception. It is very important for clinicians to review the basics of harmful medical radiation exposure since, although seldom encountered, treatment, and outcomes are time sensitive. The advent of newer technology and the widespread availability of equipment will only serve to increase the prevalence of potentially harmful medical radiation exposure. Moreover, this chapter aims to explore current multidisciplinary endeavors to provide safe and efficient use of radiation in medicine. Solely relying on the medical profession for development of safeguards against harmful medical radiation exposure would be an impossible task. This is why it is crucial for professionals such as health physicists, radiation safety enforcement officers, and policy-makers at the state, national, and international level to establish consensus guidelines aimed toward safe, reliable utilization of radiation in medicine. Part of this interdisciplinary approach needs to focus on accurate education of patients. A thorough assessment of acute radiation syndrome, including diagnosis, treatment, and prognostic indicators is also part of this chapter. Furthermore, principles of screening for, and protection from, radiation contamination are outlined. Finally, areas for further research are identified throughout the chapter. The discussion takes into account both US-based and International research and practice guidelines.