Since the 1990s, the emergence of new drugs has modified the prognosis of metastatic colorectal cancer. This malignant disease has largely benefited from the development of new drugs and new therapeutic concepts, such as oral chemotherapy or targeted biotherapy. Although a significant improvement in survival has been reached with these new therapeutic approaches, the optimal strategy remains to be defined, particularly the best sequence of drug administration. This review will focus upon new anticancer drugs, some of them with original mechanism of action, and steps towards the goal of better understanding and anticipating new treatments in colorectal carcinoma.