Abstract: Mendel's principles of inheritance postulate that only the traits coded in the genetic material (DNA) of an organism are inherited and non-genetic marks are erased and reset in the germline. However, in the past few decades, it is becoming clear that events during germ cell development and fertilization allow epigenetic marks acquired during the life time of an organism to be passed on to itsprogeny. DNMT3L is an important epigenetic regulator in mammals, integrating DNA methylation and histone modification based epigenetic circuits. Our work has shown DNMT3L to be a part of the machinery that enables inheritance of epigenetic modifications from one generation to the next. Ectopic expression of DNMT3L in Drosophila, which lacks DNMT3L and its normal interacting partners DNMT3A and DNMT3B, lead to nuclear reprogramming that was gradual and progressive, resulting in melanotic tumors that were observed when these flies were maintained for at least five generations. This misregulation of gene expression was accompanied by aberrations in the levels of active histone marks and the levels of these epigenetic aberrations (epimutations) increasedprogressively across successive generations. In light of its collaboration with Piwi, piRNAs and histone H1, I will discuss our work that shows that DNMT3L allows for inheritance of non-genetic information.