Background and Objectives There is increasing evidence that a variety of human cancers is maintained by a subset of cells, cancer stem cells (CSCs), which sustain tumor growth, underlie its malignant behavior, and possibly initiate distant metastases. The aim of this review is to evaluate the current evidence for the existence of CSCs and the implications on the present management and treatment of solid tumors. Methods A retrospective review of the English-language literature (19972010) concerning CSCs and their therapeutic implications was performed. Results CSCs are characterized by two main properties of normal stem cells: Self-renewal and differentiation, which are best assayed by serial transplantation experiments in immunodeficient mice. Cell-surface antigens that mark cell populations enriched for CSCs have been identified in various solid tumors. As such, the very existence of CSCs has vast clinical implications with regard to cancer treatment. The development of tailor-made CSC-targeted therapies (including therapies directed at these CSC-specific surface markers, and reversal of the intrinsic resistance of CSCs to chemo- and radiotherapy) entails great promises. However, normal stem cell toxicity and treatment resistance have been recognized as serious problems. Conclusion The growing evidence indicating that CSCs drive and maintain various types of solid human malignancies has important implications for the treatment of patients. However, over the years the development of CSC-targeted therapies has faced a number of potential hurdles, which must be considered carefully in order to maximize the chance that such therapies will be successful. J. Surg. Oncol. 2012; 106:209215. (c) 2012 Wiley Periodicals, Inc.