The liver is a central organ in human body that controls metabolic homeostasis, provide essential substances to the organism and allow detoxification of xenobiotics. In addition to its biological function, liver physiology is peculiar in different aspects, including its regeneration capacity. Despite the intense research performed during the last couple of decades, there are still many open questions in regard of the molecular mechanisms underlying liver function and, most importantly, liver disease. This constraint largely restricts the development of more efficient diagnostic and therapeutic strategies for the better management of the patients. In the postgenomic era, the Human Liver Initiative started in 2002 as a large-scale international collaborative initiative aiming to define a comprehensive and dynamic map of the human liver proteome.