Functional heterogeneity occurs in tumor withs a hierarchy in which tumor growth is driven by a small subset of cancer stem cells (CSCs). Like normal tissue stem cells, which are capable of self-renewal and multi-differentiation, CSCs have the ability to reconstitute tumors. CSCs also have the ability to resist chemoradiotherapy and give rise to cancer metastasis and recurrence. Therefore, eradication of CSCs will lead to complete cancer cure. In the process of developing CSC-targeted therapy, it is necessary to identify CSC-specific molecules, for which it is essential to identify definitive CSC markers and isolate CSCs with high accuracy. Although the targeting and regulation of CSCs have not yet been fully established, some reports showed that it is possible to target CSCs using molecules on which they are highly dependent or using differentiation induction similar to the normal tissue differentiation mechanism. It is expected that novel therapeutic molecules with high specificity and effectiveness will be found in the near future. In addition, the CSC concept has itself been evolving. It is necessary to clarify the exact nature of CSCs to establish a treatment strategy against them.