Despite extensive progress in basic and translational research, there are few clinically relevant predictive biomarkers for response to conventional chemotherapeutic agents(irinotecan, platinum drugs, taxanes)that can guide in the selection of an optimal chemotherapy regimen. Molecular-targeted drugs are designed to act on specific mutated/overexpressed molecules of cancer cells, and the application of predictive biomarkers for response to these drugs has been well explored. Conventional cytotoxic drugs also target-specific cellular molecules. They act on nucleic acid, enzymes related to nucleic acid metabolism, or microtubules. Now we can develop new predictive biomarkers for conventional chemotherapy using recent molecular biology techniques and molecular epidemiological studies. In this review, we summarize the investigation and application of predictive biomarkers for response to cytotoxic drugs. We focus on UDP-glucuronosyltransferase 1A1(UGT1A1), breast cancer resistance protein(BCRP), and DNA topoisomerase I (Top1)for predictive biomarkers to irinotecan therapy; glutathione S-transferase P1(GSTP1), excision repair cross-complementing 1/2(ERCC1/2), and breast cancer susceptibility gene 1/2(BRCA1/2)for response to platinum drugs; and b-tubulin, GSTP1, and thioredoxin for taxane therapy.