Colorectal cancer (CRC) is the most common malignant tumor in Western countries. Despite efforts made to implement screening programmes for early detection and treatment, still half of the patients present or will eventually develop distant metastasis. Management of advanced CRC should be discussed within an experienced multidisciplinary team, to adequately select the most appropriate systemic therapeutic option, as well as the optimal way to integrate it with surgical procedures when indicated. Disease localization and extent, resectability of primary and metastatic disease, tumor biology and dynamics, clinical symptoms, personal preferences and patient's ability to tolerate intensive chemotherapy or extensive surgical procedures are the key factors to properly design a customized treatment plan. The aim of the current manuscript is to provide synthetic practical guidelines regarding therapeutic options for advanced CRC.