The nucleus is one of the hallmarks of eukaryotic cells. The history of its discovery and characterisation is intimately entangled with that of cell biology as a discipline. Here, we provide a broad historical perspective of the nucleus, from its initial descriptions until the present. We describe the key events that led to the formulation of the chromosomal theory, the discovery of the nuclear pore complex, nucleo-cytoplasmic transport and the structure of chromatin. We also focus on the rising importance of the nuclear periphery as a key subject in nuclear research, with the characterisation of the multiple roles of nuclear lamina and the proteins involved in connecting the nuclear envelope and the cytoskeleton. Over the last decades, critical technical advancements from electron microscopy to protein structural characterisation have allowed us to gain in-depth knowledge of nuclear substructure and components, from its core to the envelope. This knowledge has set the stage for a rising challenge: understanding specialised nuclear configurations and their role in different tissues, developmental stages and disease.