Temozolomide is the primary chemotherapy used in the treatment of glioblastoma, but resistance contributes to poor prognosis. A temozolomide/siRNA synthetic lethal screen in a chemotherapy-resistant glioblastoma derived cell line identified many novel genes, including several involved in the response to reactive oxygen species (ROS). Comparison to alkylation screens conducted in E. coli and S. cerevisiae suggests that alkylation resistance mechanisms are evolutionarily conserved. Using fluorescence-based microscopy, it was found that high-dose temozolomide treatment increases ROS formation in glioma cells, as detected with the superoxide indicator dihydroethidium (DHE). For details, see article by Svilar et al. on page 1580.