Although the association between maternal smoking and low birthweight infants has been well established, the mechanisms behind reduced fetal growth are still being elucidated. While many infants are exposed to tobacco smoke in utero, not all are born growth restricted or small for gestational age. Many hypotheses have emerged to explain the differential response to in utero maternal tobacco smoke exposure (MTSE). Studies have shown that both maternal and fetal genotypes may contribute to the discrepant outcomes. However, the contribution of epigenetic changes cannot be ignored. In this review we address two important questions regarding the effect of MTSE on the fetal epigenome. First, does exposure to maternal tobacco smoke in utero alter the fetal epigenome? Secondly, could these alterations be associated with the reduced fetal growth observed with MTSE?