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The discovery that embryonic stem (ES) cell-like cells can be generated by simply over-expressing four key genes in adult somatic cells has changed the face of regenerative medicine. These induced pluripotent stem (iPS) cells have a wide range of potential uses from drug testing and in vitro disease modeling to personalized cell therapies for patients. However, prior to the realization of their potential, many issues need to be considered. One of these is the low-efficiency formation of iPSC. It has been extensively demonstrated that the somatic cell type can greatly influence reprogramming outcomes. We have shown that adipose tissue-derived cells (ADCs) can be easily isolated from adult animals and can be reprogrammed to a pluripotent state with high efficiency. Here, we describe a protocol for the high-efficiency derivation of ADCs and their subsequent use to generate mouse iPSC using Oct4, Sox2, Klf4, and cMyc retroviral vectors.