This unit describes a protocol for deriving induced pluripotent stem (iPS) cells from human fibroblast cells. Human fibroblast cells are infected with retroviral vectors expressing four transcription factors (Oct4, Sox2, Klf4, and Myc) and selected for 3 to 4 weeks under human embryonic stem (hES) cell culture conditions. iPS cell colonies are mechanically isolated using a dissection microscope and handled like hES cells thereafter. Human iPS cells share similarities with hES cells including the expression of pluripotency genes, and differentiation as embryoid bodies in vitro into three germ layers (EB) and in vivo as teratomas.