Abstract: Cytotoxic drugs are widely used in traditional antitumor chemotherapy, while the using of high dose will inevitably cause serious side effects and drug resistance. For many years, in order to make cytotoxic drugs be used safely and effectively, researchers have investigated the rational use of cytotoxic drugs, which can turn the mode of action of these drugs from killing tumor cells directly to inhibiting tumor angiogenesis. This article surveys the advances in the rational use of cytotoxic drugs.