Human somatic cells can be reprogrammed to the pluripotent state to become human-induced pluripotent stem cells (hiPSC). This reprogramming is achieved by activating signaling pathways that are expressed during early development. These pathways can be induced by ectopic expression of four transcription factors—Oct4, Sox2, Klf4, and c-Myc. Although there are many ways to deliver these transcription factors into the somatic cells, this chapter will provide protocols that can be used to generate hiPSC from lentiviruses.