Stones in arid environments are inhabited by actinobacteria of the family Geodermatophilaceae like the genera Blastococcus and Modestobacter frequently isolated from altered calcarenites. Their habitat requires adaptation to light-induced and other stresses that generate reactive oxygen species. Here, we show that representative members of the species Blastococcus saxobsidens,Geodermatophilus obscurus, and Modestobacter multiseptatus are differentially adapted to stresses associated with arid environments. Whereas B. saxobsidens was found to be sensitive to gamma radiation (D10 = 900 Gy; 10% survival at 900 Gy), M. multiseptatus was moderately (D10 = 6000 Gy) and G. obscurus was highly tolerant (D10 = 9000 Gy). A difference in resistance to high-frequency (λ value = 254 nm) UV was shown by B. saxobsidens,M. multiseptatus, and G. obscurus, being sensitive, tolerant, and highly tolerant (D10 of 6, 900, and > 3500 kJ m−2, respectively). Tolerance to desiccation, mitomycin C and hydrogen peroxide correlated with the ionizing radiation and UV resistance profiles of the three species and were correlated with the pigments synthesized. Resistance to heavy metals/metalloids did not follow the same pattern, with resistance to Ag2+ and Pb2+ being similar for B. saxobsidens,M. multiseptatus, and G. obscurus, whereas resistance to , Cr2+, or Cu2+ was greater for B. saxobsidens than for the other two species. The stress resistance profiles of M. multiseptatus and B. saxobsidens were reflected in different calcarenite colonization patterns. While M. multiseptatus was predominantly isolated from the first two millimeters of stone surface, B. saxobsidens was predominantly isolated from the deeper part of the stone where it is better protected from sun irradiation, suggesting that the response to light- and desiccation-induced oxidative stress is an important driver for niche colonization in the stone biotope.