While radiation health risks at low doses have traditionally been estimated from high-dose studies, we have reviewed recent literature and concluded that the mechanisms of action for many biological endpoints may be different at low doses from those observed at high doses; that acute doses <100 mSv may be too small to allow epidemiological detection of excess cancers given the background of naturally occurring cancers; that low-dose radiation research should use holistic approaches such as systems-based methods to develop models that define the shape of the dose-response relationship; and that these results should be combined with the latest epidemiology to produce a comprehensive understanding of radiation effects that addresses both damage, likely with a linear effect, and response, possibly with non-linear consequences. Continued research is needed to understand how radiobiology and epidemiology advances should be used to effectively model radiation worker risks.