Cancer stem-like cells (CSCs) are thought to be the major cause of tumor recurrence and metastasis due to their higher tumor initiating capacity and drug resistance. Therefore, in order to establish more efficient therapeutic strategies which could decrease the risk of recurrence and metastasis, development of the CSC-targeting therapy is urgently needed.Tumor microenvironment has recently been reported to contribute to tumor progression and resistance against therapeutic agents. Among many components of tumor microenvironment, cancer-associated fibroblasts (CAFs) are the most abundant and regarded to be critically involved in the interaction with cancer cells. CAFs could also maintain CSCs in tumors. Therefore, understanding mechanisms in which CSCs and CAFs interact would lead us to develop the efficient CSC-targeting strategy.In this review, we summarize the properties of CAFs and interaction between CSCs and CAFs. Then, we introduce some of the results obtained by our co-culture experiments of CAFs and cancer cells derived from breast cancer patient tumors. The future directions of therapeutic strategies which target CAFs are also discussed.