The microtubule-targeting agents have made significant contributions to cancer therapy over the past 50 years. The vinca alkaloids and taxanes have been used to treat a broad range of malignancies, including leukemias and lymphomas and many types of solid tumors. The taxanes have been frequently used in the treatment of advanced ovarian, breast, lung, head and neck, and prostate cancer, and they are increasingly being used in early stage disease. This chapter reviews the pharmacology, clinical indications, and toxicities associated with the vinca alkaloids and taxanes.