Metastatic colorectal cancer (mCRC) is still one of the tumor types with the highest incidence and mortality. In 2012, colorectal cancer was the second most prevalence cancer among males (9%) and the third among females (8%). In this disease, early diagnosis is important to improve treatment outcomes. However, at the time of diagnosis, about one quarter of patients already have metastases, and overall survival of these patients at 5-years survival is very low. Because of these poor statistics, the development of new drugs against specific targets, including the pathway of angiogenesis, has witnessed a remarkable increase. So, targets therapies through epidermal growth factor and its receptor and also KRAS pathways modulation acquired a main role whether in association with standard chemotherapy and radiotherapy. With the current knowledge in the field of molecular biology, including genetic mutations and polymorphisms, we know better why patients respond so differently to the same treatments. So, in the future we can develop increasingly personalized treatments to the patient and not the disease. This review aims to summarize some molecular pathways and their relation to tumor growth, as well as novel targeted developing drugs and recently approved for mCRC.