Pathology in a liver transplant setting addresses four different topics: establishment of a definite diagnosis of the liver disease before listing for transplantation, evaluation of the donor liver with regard to pre-existing diseases, in particular macrovesicular steatosis and fibrosis, assessment of the hepatectomy specimen, and post-transplant biopsy evaluation. Of these, post-transplant biopsy evaluation is the most challenging and clinically the most relevant issue. It requires fast diagnoses to facilitate specific treatment and it has to incorporate a broad spectrum of differential diagnoses. Precise knowledge about rejection, post-transplant therapy, pathology of immunosuppression, and recurrence of the initially underlying liver disease including the characteristic time peaks and atypical histological presentations (e.g., fibrosing cholestatic hepatitis) is needed to evaluate specific and combined histological pictures of liver damage. For adequate interpretation of post-transplant biopsies the hepatopathologist has to be informed about the essential clinico-anamnestic aspects such as time course, medication, imaging results, and serology.