This chapter problematizes the relation between the varied modes of knowledge production in the sciences and humanities, and the assumptions underlying the design of current e-science initiatives. Using the notion of “epistemic culture” to analyze various areas of scientific research practices, we show that current conceptions of e-science are firmly rooted in, and shaped by, computer science. This specificity limits the circulation of e-science approaches in other fields. We illustrate this using the case of women’s studies, a contrasting epistemic culture. A view of e-science through the analytic lens of epistemic cultures therefore illustrates the limitations of e-science and its potential to be reinvented.