We review the bio-activities of natural product sesquiterpenes and present the first description of their effects upon mitosis. This type of biological effect upon cells is unexpected because sesquiterpenes are believed to inactivate proteins through Michael-type additions that cause non-specific cytotoxicity. Yet, certain types of sesquiterpenes can arrest cells in mitosis as measured by cell biology, biochemical and imaging techniques. We have listed the sesquiterpenes that arrest cells in mitosis and analyzed the biological data that support those observations. In view of the biochemical complexity of mitosis, we propose that a subset of sesquiterpenes have a unique chemical structure that can target a precise protein(s) required for mitosis. Since the process of mitotic arrest precedes that of cell death, it is possible that some sesquiterpenes that are currently classified as cytotoxic might also induce a mitotic arrest. Our analysis provides a new perspective of sesquiterpene chemical biology.