The liver is the primary metastatic site in patients with colorectal cancer, and the only hope for a cure or prolonged survival in patients with liver metastases is provided by surgical resection. Advances obtained in non-resectable metastatic disease using new chemotherapeutic agents raise important questions about the use of neoadjuvant and adjuvant chemotherapy in patients with resectable liver metastases. Two major randomized studies have yielded positive results. First, a combined intra-arterial plus systemic fluoropyrimidine-based chemotherapy regimen demonstrated a relapse-free survival benefit when compared to systemic 5-fluorouracil-leucovorin therapy alone. This approach is still restricted to specialized centres, however, due to technical limitations and locoregional toxicities. Secondly, an EORTC trial demonstrated the superiority of peri-operative FOLFOX-4 chemotherapy in comparison to surgery alone. Oxaliplatin and irinotecan can induce substantial liver damage, especially steatohepatitis and vascular lesions, but the impact of these lesions on postoperative morbidity and survival remains unclear. Ongoing and planned trials will assess the addition of anti-angiogenic and anti-epidermal growth factor receptor agents to chemotherapy regimens.