Approximately 25% of patients with colorectal cancer present with metastatic disease to the liver at diagnosis, and about 50% develop liver metastases at some point during the course of the disease. Surgical resection of hepatic metastases remains the gold standard treatment for liver metastases. However, many patients with colorectal liver metastases (CRLMs) are not eligible for up-front resection. Despite advances in systemic chemotherapy, long-term survival continues to be strongly influenced by liver-directed treatments. A multidisciplinary approach is recommended for all patients, with a combination of systemic therapy and one or more liver-directed local treatments determined based on the goals of therapy. For unresectable CRLM (uCRLM), hepatic artery infusion pump therapy, stereotactic body radiation therapy (SBRT), image-guided ablation, and transarterial chemo- or radioembolization are local-regional options to consider. More recently, emerging evidence supports the use of liver transplantation in selected patients with uCRLM. This chapter reviews the spectrum of liver-directed therapies, their outcomes, and ongoing developments regarding local regional therapies for uCRLM.