Purpose of review Colon cancer is the second leading cause of cancer death in Western countries. Although most colon cancer patients will undergo curative surgery, survival, depending on the pathologic stage, varies from 30-60% for Dukes C to 60-80% for Dukes B. Until very recently, the absolute benefit for survival obtained with adjuvant therapy compared with control was about 6%. The present review analyzes the results of the new combination of 5-fluorouracil/leucovorin/oxaliplatin (MOSAIC study), the oral fluoropyrimidines, and the studies of genetic and molecular markers, attempting to identify the patients at risk of recurrence. Recent findings Both 5-fluorouracit/leucovorin/oxaliplatin and the oral fluoropyrimiclines show a statistically significant benefit of experiments treatment compared with 5-fluorouracil/ leucovorin and no treatment, respectively. A reduction of 23% in the risk of relapse (disease-free survival rates of 78.2% in the 5-fluorouracil/leucovorin/oxaliplatine arm compared with 72.9% for 5-fluorouracil/leucovorin; P = 0.002) for the former and an overall hazard ratio of 0.89 for survival (95% Cl, 0.80-0.99; P = 0.04) and 0.85 for disease-free survival (95% Cl, 0.77-0.93; P < 0.001) in favor of oral therapy compared with control. A review of the literature on translational research indicates that patients at risk of recurrence can be identified by a 23-gene signature as well as by the combination of p27, p53, and vascular endothelial growth factor molecular alterations. Summary The present review shows that adjuvant therapy of colon cancer is still improving and that the use of genetic/molecular markers together with the new targeted therapies has the potential to improve survival further.