Hepatic metastases are a frequent complication of colorectal cancer (CRC), affecting over half of all CRC patients. Resection of isolated metastases can result in long-term survival, but the majority of patients relapse, and most have unresectable disease. Hepatic arterial infusion (HAI) chemotherapy delivers high concentrations of cytotoxic agents directly to liver metastases with minimal systemic toxicities. Advances in surgical techniques, development of fully implantable pumps, and modification of drug regimens have decreased complications and improved patient tolerability. Randomized trials comparing HAI with systemic chemotherapy have demonstrated superior response rates and times to hepatic progression for unresectable disease, and have shown better times to progression and overall survival rates in the adjuvant setting following hepatic resection. HAI chemotherapy has unique toxicities, including chemical hepatitis and biliary sclerosis, which can be mitigated by the addition of dexamethasone to therapy. In an attempt to prevent extrahepatic progression, combinations of HAI with systemic chemotherapy, including newer agents such as irinotecan and oxaliplatin, are currently being investigated, with promising early results.