Biological experiments conducted in underground laboratories over the last decade have shown that life can respond to relatively small changes in the radiation background in unconventional ways. Rapid changes in cell growth, indicative of hormetic behaviour and long-term inheritable changes in antioxidant regulation have been observed in response to changes in the radiation background that should be almost undetectable to cells. Here, we summarize the recent body of underground experiments conducted to date, and outline potential mechanisms (such as cell signalling, DNA repair and antioxidant regulation) that could mediate the response of cells to low radiation backgrounds. We highlight how multigenerational studies drawing on methods well established in studying evolutionary biology are well suited for elucidating these mechanisms, especially given these changes may be mediated by epigenetic pathways. Controlled evolution experiments with model organisms, conducted in underground laboratories, can highlight the short- and long-term differences in how extremely low-dose radiation environments affect living systems, shining light on the extent to which epimutations caused by the radiation background propagate through the population. Such studies can provide a baseline for understanding the evolutionary responses of microorganisms to ionizing radiation, and provide clues for understanding the higher radiation environments around uranium mines and nuclear disaster zones, as well as those inside nuclear reactors.