Effective systemic drugs are increasingly used to treat patients with colorectal liver metastases. Recent trials have shown that chemotherapy can reduce the size of metastases that are unresectable rendering them resectable, and decrease postoperative recurrence rates in patients with initially resectable tumours. The increasing use of chemotherapy for colorectal liver metastases has raised awareness of the potential hepatotoxicities induced by systemic drugs and the effects of these drugs on outcome after hepatic resection. In this Review, we outline the rationale for the use of perioperative chemotherapy for colorectal liver metastases, associations between specific agents and patterns of liver injury, and strategies to treat patients with suspected or known chemotherapy-associated hepatotoxicity.