Recent studies highlight the tremendous potential ofhuman embryonic stem (ES) cells and their derivativesas therapeutic tools for degenerative diseases. However,derivation and culture of ES cells can induce epigeneticalterations, which can have long lasting effects on geneexpression and phenotype. Research on human andmouse stem cells indicates that developmental, can-cer-related genes, and genes regulated by genomicimprinting are particularly susceptible to changes inDNA methylation. Together with the occurrence ofgenetic alterations, epigenetic instability needs to bemonitored when considering human stem cells for thera-peutic and technological purposes. Here, we discuss themaintenance of epigenetic information in cultured stemcells and embryos and how this influences their developmental potential.