Hepatic resection remains the primary potentially curative therapeutic modality for liver metastases. The regenerative process that occurs postoperatively is a complex phenomenon, orchestrated by molecular cascades involving growth factors, cytokines, proteolytic enzymes and other proteins. Unfortunately, some of these molecules, such as hepatocyte growth factor, tumour growth factor beta and matrix metalloproteinases also promote tumour growth and may contribute to the recurrence of liver metastasis. The reactivation of dormant micrometastases or the intrahepatic accumulation of circulating malignant cells has been suggested as the responsible mechanism, although not clearly understood. Current clinical and experimental research has developed inhibitors of several regenerative molecules, attempting to treat tumour reappearance within the liver. Despite the considerable progress of the last decade, multiple queries remain to be clarified concerning liver regeneration, as well as its impact on post-hepatectomy tumour recurrence. This review describes the responsible molecular pathways and the clinical importance of post-hepatectomy liver regeneration, and investigates how the regenerative process may promote metastatic tumour recurrence.