A fundamental problem in cancer research is identification of the cell type capable of initiating and sustaining growth of the tumor – the cancer stem cell (CSC). While the existence of CSCs was first proposed over 40 years ago, only in the past decade have these cells been identified and characterized in hematological malignancies. Recent studies have now described CSCs in solid tumors of the breast and brain, raising the possibility that such cells are at the apex of all neoplastic systems. An appreciation of the biological distinctness of CSCs is crucial not only for the design of studies to understand how tumorigenic pathways operate but also for the development of specific therapies that effectively target these cells in patients.