Because cytotoxic chemotherapeutic agents have narrow therapeutic windows and large interindividual variability in pharmacokinetics/pharmacodynamics, dosing of these agents requires precise individual adjustment. Although the body-surface area (BSA) has long been used for this purpose, its effectiveness for minimizing interpatient variability in pharmacokinetics has been questioned. In this review, the factors that possibly contribute to inter-individual variability in drug response are reviewed, with a special focus on cytotoxic chemotherapeutic drugs such as platinum-containing agents, taxanes, irinotecan, and antimetabolites. Given that use of BSA fails to minimize inter-patient variability in drug response, causes inconvenience in reconstituting individual doses, and can result in human error, initial flat dosing with subsequent therapeutic drug monitoring might be a reasonable option that also has economic benefits.