The concepts of stem cells being resistant to therapy, stem-like cells existing in brain tumors, and these tumors initially responding to therapy followed by recurrence are well documented. On this foundation, a recent paper in Nature has demonstrated that CD133-expressing glioma cells in vivo and in culture are relatively resistant to radiation. The mechanism of resistance involves the cell-cycle-regulating proteins CHK1/CHK2. The data raise many questions about the details of radiobiology of stem-like cells in their native environment within tumors in vivo. These answers may lead to better optimization of radiation treatments and schedules for these patients.