Colorectal cancer (CCR), which is one of the most common causes of cancer, has 
benefited from the major advances in the understanding of the intracellular 
signaling pathways implicated in the initiation, growing and local and 
metastasis dissemination of tumor, which have occurred during the 20 past years. 
The pharmacogenomics approach, especially the determination of the genetic 
polymorphisms, tries to find prognosis and predictive biomarkers permitting to 
identify patients who could benefit from a particular treatment or those 
exhibiting higher risks of toxicity. Among the numerous biomarkers, which have 
been studied, few are currently in use in clinical practice. The phenotyping of 
DPD and UGT1A1 activities, and to a lesser extent, its genotyping, appears as 
the most useful tool in terms of prediction of toxicities induced by two major 
drugs: 5-FU and irinotecan. For oxaliplatin, the determination of the 
polymorphisms of reparases and detoxification systems such as GSTpi seems 
interesting, but its exact place should be more defined. It is in the field of 
targeted therapies that the pharmacogenomics approach seems to be the more 
relevant. KRAS mutation is a dramatic example of single nucleotide polymorphism, 
which is able to identify a priori patients that could receive or not an 
anti-EGFR monoclonal antibody such as cetuximab or panitumumab. It is obvious 
that pre-clinical identification of molecular biomarkers predictive of the 
sensitivity of the drug targets, which subsequently implicate the selection of 
patients and the rational evaluation of responses, will be the cornerstone of 
any clinical trials concerning targeted therapies. Besides the determination of 
drug target polymorphisms, it is also important to consider those related to the 
distribution and metabolism. In this area, the determination of enzymatic 
activities should recover its place besides the genomic profiling.