Colorectal cancer is one of the most common cancer types in both men and women. There are multiple treatment strategies; however, there is currently no clear strategy for therapy selection. Pharmacogenomics includes studies of variations in germline DNA, somatic mutations in the tumor genome, gene amplification, and variations in RNA expression, including epigenetic mechanisms. Pharmacogenomics promises to be a useful tool for identifying markers that can be screened in colorectal patients prior to chemotherapy selection to predict efficacy and/or toxicity. This review highlights some of the ongoing research to identify pharmacogenomic markers in colorectal cancer patients.