After all significant time, money, and the efforts expended on cancer research over the last half century, the contribution of newly developed therapeutics to improve patient survival has been limited, as these therapies have failed to prevent cancer relapses and to reach sustainable clinical responses. Cancer is heterogeneous disease and cellular heterogeneity within tumor is common. Cancer Stem Cells (CSCs) hypothesis suggests that tumors contain a small number of tumor-initiating cells within the tumor, these cells are resistant to existing cancer therapies, and they can regenerate all the cell type and metastasis in the tumor through their stem cell-like behavior. For this reason, innovative drugs which target and kill CSCs provide an attractive opportunity to improve cancer treatment. Using this original approach we are identifying and developing drugs that target and kill cancer stem cells.