The monoallelic expression of imprinted genes is regulated by DNA methylation marks that originate from the oocyte or sperm. Li et al. (2008) show in this issue of Developmental Cell that the KRAB zinc finger protein Zfp57 contributes to the embryonic maintenance of these imprints. At one locus, Zfp57 is also involved in imprint establishment. These findings provide a mechanistic interpretation for Mackay et al.’s recently reported ZFP57 mutations in patients with transient neonatal diabetes.