Background. Hepatic perfusion plays a crucial role in liver transplantation strategies, for example, when preserving procured organs with the use of machine perfusion preservation (MP) and in the case of living donor liver transplantation (LDLT). Liver hemodynamics are not yet fully understood because of insufficient knowledge on the hepatic vascular morphology and its perfusion characteristics, hampering the optimization of liver transplantation procedures. To this end, we developed computer models to simulate the complex blood circulation through the liver from the macro-scale down to the terminal micro-scale level. Methods. A combination of state-of-the-art techniques (vascular corrosion casting, micro-CT scanning up to a 2.6-mu m resolution, and image processing) led to 3D visualizations and detailed geometrical analyses of the complex architecture of the liver's 3 vascular trees, ranging from the largest vessels (macrocirculation) down to the sinusoids (microcirculation). Results. On the basis of these data, we developed various computational models (electrical analog models and 3D computational fluid dynamics models) to study the blood flow induced forces acting on the hepatic blood vessels. The latter was done for physiological blood flow through the liver as well as for livers undergoing MP or LDLT procedures. Hereby, several scenarios were simulated to study the behavior of livers in different hemodynamic circumstances. Conclusions. A novel, multi-level modeling framework was developed to simulate hepatic perfusion in support of liver transplantation strategies. We obtained unique anatomical data on the vascular architecture of both human and rat livers. These data formed the building blocks of electrical analog models of hepatic perfusion and numerical models of the liver microcirculation. The results revealed novel insights into the hemodynamic impact of liver MP and LDLT procedures as well as into the microcirculatory perfusion characteristics. The presented methodology is also applicable to other tree-like structures (eg, the biliary tree) or organs (eg, kidneys, lungs).