Embryonic stem (ES) cells are pluripotent stem cells derived from the inner cell mass of preimplantation embryos. Induced pluripotent stem (iPS) cells can be generated by somatic cell reprogramming following the exogenous expression of specific transcription factors (Oct-3/4, KLF4, SOX2, and c-Myc). Stem cell pluripotency can be defined and experimentally evaluated by assessing the ability of starting cell populations to differentiate into somatic cell types that arise from the three vertebrate germ layers: ectoderm, mesoderm, and endoderm. In addition, embryonic and induced pluripotent stem cells are characterized by the ability to undergo long-term self-renewal in vitro when cultured with growth factors provided by feeder cells or defined culture media. Pluripotent stem cell phenotypes can be modulated by chemical compounds and small bioactive molecules that enhance the proliferation or direct the differentiation of pluripotent stem cells.