Globally, the number of colorectal carcinoma-related deaths totals close to 600,000 each year, with metastatic disease representing the major cause of morbidity and mortality. The liver is the most common site of metastasis for patients diagnosed with colorectal carcinoma. Although surgical resection is the mainstay for treatment with curative intent, this option is available to a minority of patients with metastatic disease. Hepatic arterial infusion chemotherapy was developed with the intention to focus treatment on a site of difficult to control metastatic disease. In this review, we aim to present the rationale for the development of hepatic arterial infusion chemotherapy, the basic anatomic and pharmacological underpinnings of this treatment, the associated toxicities, and a brief survey of the expanding applications for this approach.