The most common site of blood-borne metastases from colorectal cancers (CRC) is the liver. Resection of (liver) metastases is a part of standard treatment of metastatic colorectal cancer. Hepatic resection is the first-line treatment of liver metastases, with 5-year survival rates between 25 and 58%. The enhanced efficacy of systemic chemotherapeutic regimens has increased tumor response rates and improved the progression-free and overall survival of patients with these malignancies. In approximately 20% of patients with initially unresectable liver metastases, the metastases may become resectable after administration of neoadjuvant chemotherapy. Unresectable liver metastases can be managed with systemic therapy and/or a variety of liver-directed techniques such as radiofrequency ablation, hepatic artery infusion, or yttrium-90 radioembolization. Our examination of the literature led us to propose a new patient-oriented algorithm to guide clinicians' decisions on the best choice of upfront therapy for CRC and synchronous liver metastases. The need for multidisciplinary consensus has become especially important for metastatic CRC.