Following the discovery that leukemic cells exhibit properties of hematopoietic stem cells, the prospective isolation of stem-like cells with high tumorigenicity has been reported for a variety of tumors. These “cancer stem cells” (CSCs) are so named because they exhibit the capacity for sustained self-renewal and possess the ability to regenerate transplanted tumor masses resembling the primary tumor in immunodeficient mice. However, the existence of CSCs remains contentious in the field of cancer biology, in part because of the application of inconsistent and inaccurate definitions and disputes over terminology. Herein, we review the discovery of CSCs, examine in detail their physical and functional characteristics, the mechanisms that lead to their formation, and how their contribution to solid tumor formation impacts cancer therapies.