In the domain of colorectal cancer treatment, this chapter offers a comprehensive examination of liver-directed therapies, particularly emphasizing the significance of hepatic arterial infusion (HAI) for managing liver metastases. The liver’s propensity to be the primary site for metastatic spread due to its unique blood supply is pivotal in determining the course of therapy. The inception of implantable pumps in the 1980s marked a revolutionary turn in the administration of chemotherapy, allowing for a sustained and localized delivery of therapeutic agents. Delving into the nuances of various chemotherapeutic drugs, the superior hepatic uptake and effectiveness of 5-Fluoro-2deoxyuridine (FUDR) over others is highlighted. The advancements in pump technologies that afford minimally invasive implantation and sophisticated safety mechanisms are also explored. Despite the potential for hepatic artery thrombosis, there is evidence of the low incidence of complications and the associated enhancement of patient quality of life, advocating for the robustness of HAI as a treatment modality. Furthermore, the narrative extends beyond colorectal cancer to discuss HAI’s application in treating other advanced primary liver malignancies, suggesting a favorable impact on patient survival outcomes. Ultimately, the intricate nature of HAI chemotherapy calls for a collaborative interdisciplinary approach to its application. Ongoing research is aimed at refining HAI’s efficacy and tolerability, with the prospect of improving patient survival and advancing the understanding of cancer therapeutics.