Cell signalling engenders cells with the capability to receive and process information from the intracellular and extracellular environments, trigger and execute biological responses, and communicate with each other. Ultimately, cell signalling is responsible for maintaining homeostasis at the cellular, tissue and systemic level. For this reason, cell signalling is a topic of intense research efforts aimed to elucidate how cells coordinate transitions between states in developing and adult organisms in physiological and pathological conditions. Here, we review current knowledge of how cell signalling operates at multiple spatial and temporal scales, focusing on how single-cell analytical techniques reveal mechanisms underpinning cell-to-cell variability, signalling plasticity, and collective cellular responses.