Microtubule poisons such as taxol and vinblastine are widely used to treat a variety of cancers. These drugs are believed to kill cells by blocking mitosis. However, there is a critical need to identify new drugs because tumors can often become refractory to treatment with existing drugs. Studies over the past decade on chromosome segregation have uncovered a plethora of novel proteins that function specifically in mitosis. Centrosomes and kinetochores are two organelles that specify formation of the spindle and the attachment of chromosomes to the spindle, respectively. The focus of this review is to highlight the kinetochore as a rich source of targets for the development of mitosis-specific drugs.