Subsequent to an initiating event, tumor promotion requires sustained cell proliferation to allow for progressive accumulation of pro-oncogenic mutations. The unique characteristics of stem cells would seem to implicate these cells as particularly suitable targets for carcinogens. Several lines of evidence suggest that tumors harbor a small population of cancer stem cells (CSC) which both give rise to the bulk of the tumor and are tumorigenic in experimental models. Mounting evidence suggests that these cells are responsible for regrowth of a tumor following unsuccessful treatment and for the establishment of metastases. The concept of CSC has been demonstrated in several human cancers including leukemia, breast, prostate, lung, and brain tumors. Taken together, the properties of CSC suggest that they are appropriate targets for cancer therapies. Such treatments would require a deep understanding of the CSC origin, molecular profile, and interaction with the local microenvironment. This report will summarize what is currently known regarding CSC, with particular emphasis on hepatic cancers, the cellular origin of liver tumors, and the role of liver stem cells and their niche in hepatocarcinogenesis.