It has been well known that inter-individual differences exist in response to chemotherapeutic drugs. A variety of factors including age, gender, intake of other drugs, and inheritance can affect the response to chemotherapeutic drugs. Development of personalized medicine, which enables physicians to tailor the dose to each patient, is urgently needed in daily clinical practice. Pharmacogenomics is one of the approaches to achieve personalized medicine and the reports of pharmacogenomics are accumulating in recent years. Furthermore, the progress of genotyping technologies has allowed for wider screening approach such as genome-wide association study (GWAS). This article reviews the current knowledge and challenges of pharmacogenomics in colorectal cancer and discusses future perspectives.