This paper builds upon historico-epistemological analyses of plasticity across the nineteenth and twentieth centuries to distinguish among uses of this notion in contemporary epigenetics. By digging into this diachronic phase of plasticity thinking, we highlight a series of historically situated understandings and pragmatic dimensions of this notion. Specifically, our analysis describes four distinct phases in plasticity thinking across the nineteenth and twentieth centuries: plasticity as chemical modification of the body by its milieu; plasticity as explanandum for the modifications of life’s (...) ontogenetic and phylogenetic substrates; plasticity as mechanistic process in need of distinct explanations in ontogeny and phylogeny; and plasticity as responsive potential to perturbations of a complex genetic system of development. These four versions of plasticity provide, in turn, the opportunity to discern synchronically the uses of this notion in epigenetic biosciences. Fleshing out these historical ramifications animating the present, we argue, highlights a fundamental epistemological disagreement at the basis of the controversies around the definition, scope, and epistemic priorities of epigenetics: how to reconcile the contemporary epistemologies of plasticity that hold epigenetic marks capable of bearing the material impression of the environment with those grounded on a strong view of plasticity as operating under genetic control? Parallel to this analysis of the epistemic space of plasticity from the nineteenth century onward, we show how these distinct modes of understanding body–environment relationships also constituted conceptual, representational, and experimental resources for understanding the entanglement between life as a biological and socially situated phenomenon. These different traces of biosocial thinking ante litteram, we conclude, provide a blueprint to interrogate today’s assumptions, values, ontologies, and political leanings behind similar attempts to interpret the biosocial nexus that links our biology with its material, social, and cultural environments. (shrink)