The genetic stability of induced pluripotent stem (iPS) cells has a significant impact on their potential use in regenerative medicine and basic research. Analysis of the genomic integrity of iPS cells suggests a tendency to develop aberrations ranging from whole chromosome trisomies to single nucleotide mutations. Furthermore, fluctuations in telomere elongation and changes in mitochondrial DNA are also observed. Some mutations may already exist in the founder cells or result from prolonged culturing, however, many of the mutations occur during the reprogramming event. Thus, great care should be given to the initial characterization and subsequent culturing of new iPS cell lines in order to avoid the use of potentially aberrant cells.