Liver fibrosis and cirrhosis resulting from long-standing liver damage represents a major health care burden worldwide. To date, there is no anti-fibrogenic agent available, making liver transplantation the only curative treatment for decompensated cirrhotic liver disease. Liver fibrosis can result from different underlying chronic liver disease, such as chronic viral infection, excessive alcohol consumption, fatty liver disease or autoimmune liver diseases. It is becoming increasingly recognised that as a result from different pathogenic mechanisms liver fibrosis must be considered as many different diseases for which individual treatment strategies need to be developed. Moreover, the pathogenic changes of both liver architecture and vascularisation in cirrhotic livers, as well as the lack of “true-to-life” in vitro models have impeded the development of an effective anti-fibrogenic drug. Thus, in order to identify an efficient anti-fibrogenic compound, novel in-vitro models mimicking the interplay between pro-fibrogenic cell populations, immune cells and, importantly, the extracellular matrix need to be developed.