Over the last two decades, network-focused approaches have become highly popular in diverse fields of biology, including neuroscience, ecology, molecular biology and genetics. While the network approach continues to grow very rapidly, some of its conceptual and methodological aspects still require a programmatic foundation. This challenge particularly concerns the question of whether a generalized account of explanatory, organisational and descriptive levels of networks can be applied universally across biological sciences. Consequently, the central focus of this theme issue will be on (...) the definition, motivation and application of key concepts in biological network science, such as levels, hierarchies, and explanatory directionality. A unification will be achieved by formulating norms for delimiting the distinctively network-topological class of explanations that connect general as well as very specific biological research questions. The impact of this theme issue is broad and encompassing, as it is highly interdisciplinary and opens a uniquely normative perspective on the foundational aspects of network-based explanations and modelling. This theme issue is intended to become a landmark publication for practical research as well as funding policy decisions, by unifying network approaches in biological sciences in terms of fundamental concepts and informing the public understanding of the network science. (shrink)