Curative resection of liver metastases from colorectal cancer is associated with improved overall survival rates, making complete resection the goal of therapy for many patients. The addition of newer, more active chemotherapeutic regimens has prolonged patient survival in those with advanced disease and increased the number of patients eligible for surgical therapy. However, concerns regarding chemotherapy-associated liver injury may have a negative impact on the ability to offer potentially curative therapy and may increase morbidity in some patients. Specific forms of liver injury have been associated with various chemotherapeutic regimens, including steatosis and steatohepatitis with prolonged fluorouracil and irinotecan therapy, and sinusoidal injury with oxaliplatin-based regimens. While the histologic association appears likely, the contribution of chemotherapy-associated hepatotoxicity to postoperative morbidity remains ill defined.