Crosstalk between sympathetic nerves and immune cells is increasingly recognised as a crucial process for protection and recovery from viral infections and cancers. Yet, how sympathetic signalling alters immunity is still relatively poorly understood. We are using contemporary neuroscience tools to map neuron subsets that innervate lymphoid organs and tumours and define mechanisms of sympathetic neuroimmune crosstalk. Using chemogenetic and transgenic mouse models, intravital imaging, single cell transcriptomics and quantitative spatial imaging we describe dynamic modulation of neuronal functions by immune responses and reciprocal regulation of immune responses by sympathetic neurons.