Resolving the molecular mechanisms of radiation oncogenesis represents an important but daunting challenge in radiation research. This brief review outlines the principal oncogenic mechanisms that need to be considered in the context of radiation effects on the genome, how these might relate to specific gene and chromosomal changes relevant to neoplasia and the possible implications of such knowledge for the modelling of cancer risk. The long-term application of this mechanistic knowledge to the determination of tumour causality and for the assessment of individual cancer risk is also briefly discussed.