The liver has the exceptional ability to rapidly regenerate and restore function following tissue damage. This phenomenon has fascinated many clinicians and scientists throughout history. However, the precise mechanisms behind liver regeneration have not yet been fully elucidated. Macrophages (Macs) have been shown to play a key role in regeneration. Nonetheless, the role of liver-resident Kupffer cells (KCs) versus recruited Macs (rMacs) is unclear, as until now we lacked the tools to distinguish between these two types of phagocytes. Moreover, studies have mainly focused on hepatocyte proliferation. Within the liver KCs are in contact with liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs) and hepatocytes. These cells can be thought of as a liver module, which needs to be rebuilt during liver regeneration. In this project, I will take a modular approach and propose the use of innovative tools to study cell-cell cross-talk and conclusively determine the signals driving the formation of new liver modules. The findings of this research will be of clinical relevance, as a better understanding of the mechanisms underpinning liver regeneration may yield therapies to boost liver regeneration and prevent the need for transplantation.