The risk of ionizing radiation from diagnostic imaging has been a popular topic in the radiology literature and lay press. Communicating the magnitude of risk to patients and caregivers is problematic because of the uncertainty in estimates derived principally from epidemiological studies of large populations, and alternative approaches are needed to provide a scientific basis for personalized risk estimates. The underlying patient disease and life expectancy greatly influence risk projections. Research into the biological mechanisms of radiation-induced DNA damage and repair challenges the linear no-threshold dose-response assumption and reveals that individuals vary in sensitivity to radiation. Studies of decision-making psychology show that individuals are highly susceptible to irrational biases when judging risks. Truly informed medical decision-making that respects patient autonomy requires appropriate framing of radiation risks in perspective with other risks and with the benefits of imaging. To follow the principles of personalized medicine and treat patients according to their specific phenotypic and personality profiles, diagnostic imaging should optimally be tailored not only to patient size, body region and clinical indication, but also to underlying disease conditions, radio-sensitivity and risk perception and preferences that vary among individuals.