Of the agents available in the treatment of both solid and hematologic cancers, microtubule-targeted agents are among the most widely used and exploiting other mechanisms involving the microtubule and its role in mitosis is an area of continued interest. This review will focus on novel microtubule-targeted agents, both recently approved (eg, ixabepilone and eribulin) and in later-stage clinical trials, and kinase inhibitors that aim to directly inhibit the mitotic spindle, such as the aurora kinase, pololike kinase, and kinsein-spindle protein inhibitors.