The development of novel approaches in liver surgery in the last decade has saved the lives of a large number of patients via resection of liver tumours previously thought to be non-resectable. Concurrently, living donor liver transplantation has emerged as one of the ways of lowering mortality on the waiting lists. These breakthroughs demanded a rigorous understanding of the mechanisms of liver regeneration after partial hepatectomy. Based on our previous studies on blood platelets and cold ischaemic injury, platelets and serotonin have attracted attention due to their theoretical potential contribution to liver regeneration. Both platelets and serotonin have been proven to be crucially involved in liver regeneration after partial hepatectomy. This review article provides an overview on the process of liver regeneration, with emphasis on its molecular basis and the coordinate contribution of several cells to restoring the organ's original volume and function. The role of platelets and serotonin is highlighted as novel contributors in this process.