Since small subpopulations of CSCs were identified from blood mononuclear cells in human acute myeloid leukemia in 1997, it has attracted a great deal of attention recently benefited with advances in SC biology as well as the revisited concept of cell quiescence or tumor dormancy. Also, as the reason why a small population of cancer cells referred to CSCs have received particular attention, CSCs were responsible for acquiring stem cell-like properties and becoming the main cause of tumor propagation and metastasis as well as chemotherapeutic or radiation resistance. Though many CSC-targeted therapy methods were expected to cure or prevent cancer by eradicating CSCs, it has not come true clinically yet. Since the identification of CSC-specific markers, the isolation and characterization of CSCs from malignant tissues, and targeting strategies for the destruction of CSCs might provide a novel opportunity for cancer research, huge efforts are now on progress. Repositioning research for metformin, CQ, PPI, APA, and Shh inhibitor might provide unexpected discovery for chemoquiescence in the near future, the expected translational impact of the “old drugs-new uses” repurposing strategy to open a new CSC-targeted chemoprevention era (Fig. 23.2) (Vazquez-Martin et al. 2011; Del Barco et al. 2011). Ongoing chemopreventive, neoadjuvant, and adjuvant trials should definitely establish whether metformin’s ability to kill the “dandelion root” beneath the “cancer soil” likely exceeds metformin-related dangers of hormesis (Del Barco et al. 2011). From our investigation as shown in Fig. 23.1, CQ can be one of the most effective and safe sensitizers for cancer therapies based on results of our and other investigations focused on the changes of tumorsphere after CQ. Taken together, the efficacy of conventional cancer therapies can be dramatically enhanced with the combination of CQ and its analogs (Kimura et al. 2013; Solomon and Lee 2009; Maycotte et al. 2012), with the possibility of achievement of chemoquiescence in the near future after extensive clinical investigation.