The present invention provides drug response predictors and biomarkers useful for assessing the responsiveness of a subject to treatment with one or more target drugs of interest, such as 5-fluorouracil (5-FU), irinotecan, and/or oxaliplatin. In particular, the invention provides methods useful in determining whether a subject is sensitive or resistant to a target drug by, e.g., measuring the expression level of one or more biomarkers of sensitivity and/or resistance to the drug in a biological sample obtained from the subject. The invention further features devices and kits for assessing target drug responsiveness in a subject, for example, by determining the expression level of such biomarkers.