The position of the nucleus within cells is a key event during cell migration. The movement and positioning of the nucleus strongly impacts cell migration. Notably, the last two years largely contributed to emphasise the dynamicity of the nucleus-cytoskeleton interactions that occur during cell migration. Nuclei are under continuous tension from opposing intracellular forces and its tether to the cytoskeleton can be regulated at different levels. Interestingly, it was showed how nuclear positioning is highly related to cell function. In most migrating cells, including cancer cells, the nucleus can be the rate limiting step of cell migration and is placed away from the leading edge. By contrast, leukocytes position their nucleus close to the lamellipodia at the leading edge, and the nucleus contributes to drilling through the endothelium. Differences in cell migration in 2D versus 3D environments are also evident. The mechanisms and forces at play during nuclear positioning and translocation are clearly affected by the nature of the substrate. As such nuclear positioning during cell migration can vary between cell types and environments. In this review we aim to give an overview of the latest discoveries in the field revealing how nuclear positioning is tightly regulated, not only by intrinsic nuclear properties, such as deformability, nuclear envelope content or nucleus-cytoskeleton connectivity, but also by the microenvironment.