Primary human hepatocytes and cell lines are commonly used to assess the toxicity of chemicals. However, embryonic stem cells and induced pluripotent stem cell-derived hepatocytes are potentially more attractive for preclinical purposes, given their unlimited expansion capability. The expanded application of stem cells combined with 3D culture systems using a hepatic multiple-cell society, ex vivo systems using humanized rodent livers, and in vivo systems could lead to improved toxicity and preclinical studies.