The review article by Cerneckis, Cai, and Shi provides an in-depth overview of induced pluripotent stem cells (iPSCs) technology, highlighting its molecular mechanisms and applications. iPSCs have revolutionized in vitro research and regenerative medicine due to their ability to expand indefinitely, undergo genetic engineering, and differentiate into various somatic cell types. The authors discuss the pivotal discoveries that led to the successful generation of iPSCs, including the reprogramming of somatic cell nuclei. They explore the molecular mechanisms and dynamics of somatic cell reprogramming, emphasizing the roles of transcription factors, chromatin dynamics, and DNA methylation. The review also covers various methods for inducing pluripotency, such as viral and non-viral vectors, and small-molecule compounds. The article further discusses the versatile applications of iPSCs, including modeling human development and diseases, drug screening, and cell therapy development. iPSC-derived cellular models, ranging from mono-cultures to complex three-dimensional organoids, are used to elucidate mechanisms of human development and diseases. Examples of disease-specific phenotypes modeled using iPSC-derived cells include neurological disorders, COVID-19, and cancer. The review also highlights the potential of iPSC-derived cells in high-throughput drug screening and toxicity studies. Finally, the authors address the challenges and limitations of iPSC technology, such as the persistence of somatic cell signatures and the need for maturation of iPSC-derived cells to achieve functional maturity. They emphasize the importance of creating physiologically relevant environments and paracrine signaling to enhance the maturation of iPSC-derived cells. Overall, the review underscores the immense potential of iPSC technology in advancing in vitro research and therapeutic development.The review article by Cerneckis, Cai, and Shi provides an in-depth overview of induced pluripotent stem cells (iPSCs) technology, highlighting its molecular mechanisms and applications. iPSCs have revolutionized in vitro research and regenerative medicine due to their ability to expand indefinitely, undergo genetic engineering, and differentiate into various somatic cell types. The authors discuss the pivotal discoveries that led to the successful generation of iPSCs, including the reprogramming of somatic cell nuclei. They explore the molecular mechanisms and dynamics of somatic cell reprogramming, emphasizing the roles of transcription factors, chromatin dynamics, and DNA methylation. The review also covers various methods for inducing pluripotency, such as viral and non-viral vectors, and small-molecule compounds. The article further discusses the versatile applications of iPSCs, including modeling human development and diseases, drug screening, and cell therapy development. iPSC-derived cellular models, ranging from mono-cultures to complex three-dimensional organoids, are used to elucidate mechanisms of human development and diseases. Examples of disease-specific phenotypes modeled using iPSC-derived cells include neurological disorders, COVID-19, and cancer. The review also highlights the potential of iPSC-derived cells in high-throughput drug screening and toxicity studies. Finally, the authors address the challenges and limitations of iPSC technology, such as the persistence of somatic cell signatures and the need for maturation of iPSC-derived cells to achieve functional maturity. They emphasize the importance of creating physiologically relevant environments and paracrine signaling to enhance the maturation of iPSC-derived cells. Overall, the review underscores the immense potential of iPSC technology in advancing in vitro research and therapeutic development.