Recent discoveries show that early in life effects often have long-lasting influences, sometimes even spanning several generations. Such intergenerational effects of early life events appear not easily reconcilable with strict genetic inheritance. However, an integrative evolutionary medicine of early life effects needs a sound view of inheritance in development and evolution. Here, we show how to articulate the gene-centred and non-gene-centred visions of inheritance. We first recall the coexistence of two gene concepts in scientific discussions, a statistical one (focused on patterns of parent–offspring resemblance, and implicitly including non-DNA-sequence-based resemblance), and a molecular one (based on the DNA sequence). We then show how all the different mechanisms of inheritance recently discovered can be integrated into an inclusive theory of evolution where different mechanisms would enable adaptation to changing environments at different timescales. One surprising consequence of this integrative vision of inheritance is that early in life effects start much earlier than fertilization.This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.