In mammals, the maternal and the paternal genome are not functionally equivalent and are both required for embryonic and postnatal development. The genome is organised differently in the oocyte as compared to sperm, in which the DNA is tightly packaged with protamines rather than with histones. The requirement of both the parental genomes for normal development is a consequence of differential epigenetic marking in oogenesis and spermatogenesis, at the regulatory elements that control genomic imprinting. These germ line-derived marks of DNA methylation are resistant to the global waves of demethylation that occur following fertilisation, and bring about the parental allele-specific expression of imprinted genes during development and after birth. Perturbation of the differential organisation of the maternally and paternally derived genomes, before fertilisation, or in the early embryo, can give rise to aberrant growth and developmental disorders in humans.