Over the past 20 years, the explosion of research on epigenetics has provided a mechanistic basis for how the environment influences gene expression in living organisms, without acting on the nucleotide sequence of DNA. Epigenetic characters are carried by chemical modifications of chromatin (DNA methylation, post-translational modifications of histones) and/or by RNAs. Their role is fundamental in the determinism of cellular identity during embryonic development. They also shape the response of somatic cells to endogenous stimuli (e.g. hormones, growth factors, metabolites, cytokines) or exogenous stimuli (e.g. nutrients, toxic chemicals, microbial molecules, stress).1 Some changes in chromatin are inheritable during cell divisions, allowing a stable transcriptional reprogramming of somatic cells over time. But can epigenetic variation be transmitted from a whole organism to the descendants? In other words, can epigenetic variation reach the germinal cells and cross the barrier of sexual reproduction, thus perpetuating new phenotypes induced by the environment, in absence of any genetic mutation? This “Lamarckian” question is the source of many interests and debates. While transgenerational epigenetic heritability is well established in plants,2 its existence in animals still raises many questions.3,4 Hence, it is of importance to generate experimental models enabling to follow complex phenotypes, together with genetic and epigenetic modifications, for many generations. Some insect species can be used as such models, as they offer several advantages over mammalian models, including short generation times, ethical acceptability, and a potential for studying complex parameters (e.g. longevity, fertility, gender ratio, responses to environmental stresses).5 Insect models are also powerful for studying microbial infections and host resistance against microbes. It should be emphasized that pathogens are capable of acting on the epigenetic machinery of their host, and conversely, epigenetic regulators have been identified as actors of the host responses to infections.6,7 There is also an epigenetic component in the mechanistic basis of inter-individual differences in immune responses to pathogens.8 It is therefore tempting to speculate that epigenetic mechanisms could play a role in the transmission of protective defenses against pathogens from parents to offspring. In this issue of Virulence, 9 Mukherjee et al. investigates this fascinating hypothesis by using the larva of the greater wax moth Galleria mellonella as a model host to study the transmission of the resistance against the entomopathogen Bacillus thuringiensis.