Modern radiotherapy is being driven more by technology than biology and continues to show small incremental improvements in patient outcome. Yet there are some biological concepts, such as the stem cell hypothesis, that question the ability of radiation to ever cure the more common solid tumors. At the conclusion of this activity, the learner will be able to do the following: 1. Explain the implications of stem cell biology for radiotherapy and question the current paradigm of treatment improvements. 2. Summarize the data on the multitude of different fractionation schemes in clinical use and their biological rationale. 3. Explain the concept of low dose hyperradiosensitivity and decide whether there is a clinical niche to exploit this process. 4. Describe the use of radiosensitizers and whether they will have a role to play in radiation treatment.