It has been demonstrated originally in plants that phenotypic traits, such as floral symmetry, can be caused by changes of methylation patterns of specific genes. Such traits can be transgenerationally inherited for multiple generations and remain associated with cytosine methylation patterns. Whether genomic methylation may also contribute to epigenetic inheritance across generations in vertebrates and notably in mammals is still more controversial. One reason for this tentativeness is the dual occurrence of global genomic de-methylation first in pre-implantation embryos and subsequently in primordial germ cells (PGCs) of mammals. Although gene focused cases of epigenetic inheritance associated with genomic DNA methylation have been well studied mostly in rodents (such as imprinted genes and the Agouti viable yellow, A^vy, allele), it is still a matter of debate whether genomic DNA methylation may provide a more general mechanism for the epigenetic inheritance of acquired traits across generations. We review the current literature on this topic with a focus on the potential role of DNA methylation for epigenetic inheritance across generations in mammals.