Common DNA sequence variants inadequately explain variability in fat mass among individuals. Abnormal body weights are characteristic of specific imprinted-gene disorders. However, the relevance of imprinted genes to our understanding of obesity among the general population is uncertain. Hitherto unidentified imprinted genes and epigenetic mosaicism are two of the challenges for this emerging field of epigenetics. Subtle epigenetic differences in imprinted genes and gene networks are likely to be present among cells, tissues and individuals. In order to advance obesity research it will be necessary to use genome-wide, next-generation sequencing approaches that allow the detection of such epigenetic differences.