Abstract: Traditional antitumor drugs are cytotoxic chemotherapeutic drugs that can directly kill tumor cells and inhibit the growth and proliferation of tumor cells. Modern chemotherapy for tumors was initiated by use of nitrogen mustard to treat lymphomas in 1946, which was derived from mustard gas. Starting with nitrogen mustard, many kinds of anti-tumor drugs, including alkylating agents, anti-metabolism drugs, anti-tumor antibiotics, and anti-tumor plant drugs, have been successively developed for clinical treatment. Traditional antitumor drugs are the cornerstone of tumor chemotherapy and play important roles in the comprehensive treatment and neoadjuvant therapy of malignant tumors. In recent years, the combination of traditional antitumor drugs with molecular targeted therapy, immunotherapy, and radiotherapy has greatly improved the survival rate of tumor patients. With the deepening understanding of tumor genome as well as tumor initiation and promotion, the concepts of precision medicine and individualized treatment have been proposed and achieved success in clinical practice. In this context, the strategies leading to personalized therapy with traditional anti-tumor drugs also need to be further studied and optimized. This review summarized the recent clinical application and research progress of traditional antitumor drugs.