Colorectal cancer is an important disease of the modern world, generating significant mortality and morbidity rates. Its therapy, although considerably improved, continues to be unhelpful for a large percentage of patients, especially for those in advanced stages. This justifies the efforts toward producing new therapies, as well as for stratifying patients according to risk factors and prediction of therapeutic response. In this respect, the contributions of modern science are essential for defining the most intimate mechanisms and players of tumorigenesis and for proposing new biomarkers. The study of antitumor immune responses has revealed new insights into the tumor microenvironment, leading to the development of vaccines and adoptive transfer of immunocompetent cells. Circulating tumor cells are a real opportunity to detect early relapses and to define risk categories, while miRNAs, a family of small non-coding RNA implicated in regulation of gene expression, evolved as a new class of biomarkers with high potential for diagnosis, prognosis and prediction of colorectal cancers.