Liver regeneration is a fascinating and complex process with many medical implications. An important component of this regenerative process is the hepatic progenitor cell (HPC). These appealing cells are able to participate in the renewal of hepatocytes and cholangiocytes when the normal homeostatic regeneration is exhausted. Moreover, the HPC niche is of vital importance toward the activation, differentiation, and proliferation of the HPC. This niche provides a rich microenvironment for the regulation of the HPC, thanks to the intercellular secretion of molecules. New findings indicate that the regenerative possibilities in the liver could provide a diverse basis for therapeutic targets.