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Since August Weismann (1834-1914) formulated the distinction between innate and acquired characteristics at the end of the 19th century, the debate relating to the inheritance of acquired traits has raised many controversies in the scientific community. Following convincing arguments against (e.g. William Bateson) this debate was then set aside by the majority of the scientific community. However, a number of epigenetic phenomena involving RNA, histone modification or DNA methylation in many organisms have renewed interest in this area. Transgenerational effects likely have wide-ranging implications for human health, biological adaptation and evolution, however their mechanism and biology remain poorly understood. We recently demonstrated that a germline nuclear small RNA/chromatin pathway can maintain epi-allelic inheritance for many generations in C. elegans. This is a first in animals. We named this phenomenon RNA-induced epigenetic silencing (RNAe). We are currently further characterizing the mechanism of RNAe. In addition, we are testing the hypothesis that RNAe provides a transgenerational memory of the environment (“Lamarckism”). We are currently exploring related phenomena in mice. We are also working towards establishing iPS cells differentiating into germ cells as a model to study the mechanism of transgenerational epigenetic inheritance.