Hypoxia-specific cytotoxins have long exhibited considerable promise for treating hypoxic tumors, however recent negative results in large scale clinical trials have highlighted the importance of selecting patients who are most likely to respond using hypoxia imaging methods. This review looks at the available hypoxia-specific cytotoxins and describes how existing hypoxia imaging methods can be best used to predict which tumors will respond. It then surveys prior studies which combine hypoxia-selective cytotoxin treatment with hypoxia imaging, and finally concludes with a discussion of what lessons can be learnt from previous experiences in order to improve the use of these cytotoxic agents in future clinical evaluations.