Since the discovery of the segmented shape of the neutrophil nucleus, scientists have pondered its physiological relevance. Yet, to this day, neither the functional relevance nor the molecular mechanisms underlying the segmentation of the neutrophil nucleus are fully understood. Some experimental evidence supports a role of nuclear segmentation in efficient neutrophil migration but its impact on key neutrophil functions, such as phagocytosis, degranulation or production of reactive oxygen species, remains unclear. Nonetheless, the role of nuclear shape in remodelling chromatin and regulating gene expression has high potential for biological and translational relevance. This Review aims to compile and connect the current studies on the neutrophil nucleus, while also discussing studies in other cell types that could inform us about the relevance or mechanisms of nuclear segmentation.