The digital can be understood as both the precondition for as well as the functional principle of a specific media technology founded on difference-based and difference-producing computing operations carried out by machines. It is thus always already the product of marking difference, with the analog colloquially positioned as its Other. The difference inherent in the binary duality at the heart of computing technology is not the only decisive factor in this context; rather, digital cultures are constituted by a matrix of differentiations that inscribe themselves on different levels (technical, political, material-discursive, interactive, etc.) in profiles, databases, and network structures, on (social media) platforms and services, and that include the socio-technical practices associated with them. Differences are thus not only dissimilarities, but they can also be understood as powerful processes of demarcation that order, classify, and hierarchize. At the same time, the production of difference opens up horizons for the possibility of politicizing these very differences, a process which becomes visible both on the level of the medium as well as in the socio-cultural context. The analysis, reconstruction, deconstruction, and diffraction of such processes can make the multifaceted and intertwined markers of difference and their social and cultural settings visible and negotiable. This leads to the following key questions guiding the Special Issue: Which differences are amplified or even created by efforts to make meaning and matter machine-readable? To what extent does the digital also draw into question and (re)configure meaningful differentiations and differences? To discuss these topics, the Special Issue focuses on three dimensions of the relationship between difference and the digital.