The Life Span Study of atomic bomb survivors includes residents of Hiroshima and Nagasaki, Japan, who were located within 10 km of the hypocenter at the time of the bombings in 1945, and a matched sample of Hiroshima and Nagasaki residents who were not in either city at the time of the bombings. Radiation risk estimates from the Life Span Study are used to inform policies for radiological protection in occupational, medical, and public health settings, as well as for survivors’ welfare. Analyses of Life Span Study data have historically motivated the development of now-standard statistical methods to estimate radiation risk, including dose-response modeling of event-time outcomes and accounting for measurement error in radiation doses. However, challenges remain with respect to estimating radiation risk at lower doses, including the potential impact of unmeasured confounding and competing risks that arise with life-long follow-up. I will overview these challenges, summarize the recent development of modern methods to overcome them (including sensitivity analyses for multiple comparisons based on evidence factors), and introduce opportunities for future research and collaboration.