Life revolves around death. The process of programmed cell death also called cellular suicide, is a highly regulated mechanism that is important during (embryonic) development and tissue homeostasis. The most well-studied type of programmed cell death is necroptosis, which features characteristics of both apoptosis and necrosis. However, due to suboptimal experimental animal and cell line models, detailed knowledge of these processes is still largely unknown. The work in this thesis describes how different types of programmed cell death play a role in cholangiopathies, liver cancer, and liver transplantation. For this, a 3- dimensional organoid culture method to grow and expand cholangiocyte progenitors from healthy donors, patients suffering from cholangiopathies, and cholangiocarcinoma, has been used (Part I). Furthermore, the mechanism of programmed cell death in liver ischemia-reperfusion injury during liver transplantation is described, based on patients’ biopsies and human cholangiocyte organoids culture (Part II)