Resumen: There are still a number of limitations to the full use of therapeutic drug monitoring (TDM) to optimize chemotherapy in oncology. Probably the most important ones arise from the conservatism of clinical practice and the lack of training of physicians in pharmacokinetics (PK). Pharmacogenetics and biomarkers are being incorporated much faster, although the evidence for them is less at present, perhaps because of the lack of training of physicians in quantitative PK approaches rather than remembering clinical facts. Therapy with methotrexate, carboplatin, irinotecan, taxanes, busulfan, 5-fluorouracil, tyrosine kinase inhibitors, and other drugs can be optimized through TDM. In some cases, TDM is used mainly to control toxicity, but it is also useful sometimes to maximize efficacy. Anticancer therapy is best done in a comprehensive manner, incorporating approximate tools for each type and tumor stage. Surgery, radiotherapy, and chemotherapy each have their place. Achieving specific optimal therapeutic target goals for each patient can be feasible, as target ranges of serum drug concentrations are becoming rapidly available. This chapter summarizes the existing evidence concerning the use of TDM in the management of antineoplastic drug therapy.