Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by ectopic expression of transcription factors Oct4, Sox2, Klf4 and cMyc. Recent advancements have shown that small-molecule compounds can induce pluripotency, indicating that cell fate can be regulated by direct manipulation of intrinsic cell signaling pathways, thereby innovating our current understanding of reprogramming. The fact that lineage specifiers can induce pluripotency suggests that the pluripotent state is a fine balance between competing differentiation forces. Dissection of pluripotent roadmaps indicates that reprogramming is a process of reverse development, involving a series of complicated and distinct reprogramming stages. Evidence from mouse iPSC transplantation studies demonstrated that some certain but not all cells derived from iPSCs are immunogenic. These studies provide new ways to minimize reprogramming-induced abnormalities and maximize reprogramming efficiency to facilitate clinical development and use of iPSCs.