Increasing evidence suggests that many types of cancers contain a population of cells that display stem cell properties. These cells are called cancer stem cells (CSCs). They are virtually resistant to radiation, and may contribute to treatment resistance and recurrence. Therefore, therapies specifically targeting CSCs will likely be needed for complete tumor eradication. In this article, we review published reports identifying the mechanisms of radioresistance of CSCs, potential markers that predict response to radiotherapy and potential therapies targeting CSCs, when using radiotherapy for treatment. According to the published reports, the main mechanisms of radioresistance of CSCs compared to non-CSCs are self-renewal capacity, DNA-repair capacity and enhanced reactive oxygen species defenses. Many kinds of cancers have several cell-surface markers, such as cluster of differentiation (CD)133 and CD144, and these markers appear to be potential prognostic factors for treatment outcomes. Concerning therapeutic targets for CSCs, several reports have indicated that pathways of self-renewal, the CSC niche and several signal transduction pathways are potential targets for CSCs. Other reports have indicated that several new therapies, such as carbon ion radiotherapy and internal radiotherapy with copper-64-diacetyl-bis (N4-methythiosemicarbazone) ((64)Cu-ATSM), appear to be promising treatments that target CSCs. Further elucidation of pathways that regulate CSCs may provide insights into the identification of other potential therapeutic targets and development of novel innovative therapies.