The large-scale generation and integration of genomic, proteomic, signalling and metabolomic data are increasingly allowing the construction of complex networks that provide a new framework for understanding the molecular basis of physiological or pathophysiological states. Network-based drug discovery aims to harness this knowledge to investigate and understand the impact of interventions, such as candidate drugs, on the molecular networks that define these states. In this article, we describe how such an approach offers a novel way to understand biology, characterize disease and ultimately develop improved therapies, and discuss the challenges to realizing these goals.