The current understanding of cellular responses to ionizing radiation fuses traditional radiobiological concepts with recent insight into underlying molecular mechanisms. Cell cycle arrest, induction of specific cascades of genes, and activation of DNA repair mechanisms have been reported after radiation exposure. Of particular importance is the mitogen-activated protein (MAP) kinase signaling pathway, in which the ras and raf oncogenes participate. Both of these genes have been implicated in the cellular resistance to killing by ionizing radiation. Furthermore, regulated NF-gammaB transcriptional activation may be important for the pleiotrophic responses of cells to ionizing radiation. Disruption of this signaling cascade may contribute to the radiation sensitivity syndrome seen in ataxia telangiectasia. In this review, these pathways are consolidated into ionizing radiation signal transduction pathways that lead from the cell membrane/cytosol to the nuclear DNA.