This chapter discusses the advantages and disadvantages of stem cell technology and highlights established applications. It examines the hurdles for replacing primary liver tissue in drug development, disease modeling, and regenerative medicine. Pluripotent stem cells and induced pluripotent stem cells have the potential to generate all cell types of our body. Adult stem cell-derived liver organoids have the potential to excel at a wide variety of applications. The technique combines the advantages of high expansion potential, high genetic stability, and generation of functionally mature cells. Primary human hepatocytes are the current gold standard for liver in vitro assays. Pharmaceutical compounds and their metabolites can directly damage liver tissue. Regenerative medicine has always been a key aspect in the development of stem cell-derived liver tissue. The ultimate goal of stem cell-based liver therapy is autologous transplantation of healthy liver tissue.