It is widely accepted that cancer is a disease of stem cells. Definite evidence suggests that tumors harbor a small population of cancer stem cells (CSC) that 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, pancreas, colon and brain tumors. Recently, several studies have demonstrated that liver cancer, like other tumors, are derived from a small population of liver cancer stem/progenitor cells. Although still controversial, Liver CSC will likely become the most crucial target in the treatment of liver cancer, and a thorough understanding of its origin, molecular profile and particularly of how the Liver CSC differs from the normal stem cells, might allow it to be targeted selectively and eliminated, thus improving therapeutic outcome. In this review we will summarize the recent evidence for Liver CSC, the relationship between normal and liver stem cells, and the possibility that transformation of different cell types in the liver may generate different types of liver cancers.