SummaryThe mapping of signalling networks is one of biology's most important goals. However, given their size, complexity and dynamic nature, obtaining comprehensive descriptions of these networks has proven extremely challenging. A fast and cost‐effective means to infer connectivity between genes on a systems‐level is by quantifying the similarity between high‐dimensional cellular phenotypes following systematic gene depletion. This review describes the methodology used to map signalling networks using data generated in the context of RNAi screens.