Induced pluripotent stem (iPS) cells were created from mouse fibroblasts by induced expression of Yamanaka factors, Oct3/4, Sox2, Klf4, and c-Myc. This technique has quickly resulted in an exponential increase in the amount of pluripotency studies, and has provided a valuable tool in regenerative medicine. At the same time, many methodologies to generate iPS cells have been reported, and are comprised mainly of viral methods and non-viral methods. Although viral methods may not be applicable for clinical applications, various nonviral methods have been reported in recent years, including DNA vector-based approaches, transfection of mRNA, transduction of reprogramming proteins, and use of small molecule compounds. This review summarizes and evaluates these non-viral methods.