ALT Liver disease affects more than two billion people, and there are currently only limited therapeutic options. Particularly relevant are non-alcoholic fatty liver disease (NAFLD - which affects an astounding quarter of the adult world-wide population), and liver cancer ( representing the third leading cause of cancer mortality). A detailed understanding of the liver’s biology under homeostatic and pathological conditions provides will provide an informed foundation for developing targeted and more effective therapies. The application of single cell-based and other novel ‘omics’ technologies has opened the door to a deeper understanding of the underlying pathomechanisms and allows to closely link basic science and clinical studies. These multi-disciplinary approaches can provide essential information to build a framework for the development of novel diagnostic and therapeutic approaches.