Hepatic artery infusion (HAI) chemotherapy is a locoregional therapy for colorectal cancer liver metastasis that has been available since the 1980s. Multiple clinical trials have demonstrated the safety and efficacy of HAI with higher response rates compared to systemic chemotherapy alone. Clinical trials have shown the benefit of using HAI as a bridge to conversion to resection at a higher rate than systemic chemotherapy alone with rates as high as 60% in heavily pretreated patients. HAI in combination with systemic chemotherapy has also been associated with prolonged recurrence free survival and overall survival in the adjuvant setting. Specifically, the addition of HAI continues to show a benefit in prolonging overall survival, despite increased effectiveness of modern systemic chemotherapy (i.e., oxaliplatin and irinotecan). Lower recurrence and improved survival rates associated with HAI and systemic chemotherapy persist regardless of RAS mutational status.