Induced pluripotent stem (iPS) cells were first generated from fibroblasts by exogenously expressing four transcription factors: KLF4, c-Myc, Oct-4, and SOX2. However, somatic cell reprogramming can be inefficient, and the use of viral vectors can complicate their therapeutic potential. Thus, bioactive small molecules are important tools for optimizing iPS cell generation and research. Compounds such as Thiazovivin can be added to culture media to enhance the efficiency of iPS cell generation. Chromatin modifying small molecules, such as those that target histone deacetylases (HDACs) or methyltransferases, can also aid in somatic cell reprogramming by opening chromatin and promoting the transcription of pluripotency genes. In fact, following epigenetic changes induced by Valproic Acid, a HDAC inhibitor, iPS cells can be generated from somatic cells with the introduction of only Oct-4 and SOX2. Recent reports indicate that small molecules can also replace the function of particular transcription factors. For example, Kenpaullone, a Cyclin Dependent Kinase and GSK-3 beta inhibitor, can replace KLF4. Tocris provides a complete range of small molecules to optimize somatic cell reprogramming and reduce the need for viral-mediated transduction of transcription factors.