Antimitotic agents that bind to tubulin and disrupt microtubule dynamics, such as vinca alkaloids and taxanes, are an integral part of the treatment of many human cancers. Unfortunately the clinical success of these agents can be severely hindered by the emergence of drug resistant tumour cells. In recent years interest has focused on alterations in the cellular target of antimicrotubule compounds, the tubulin/ microtubule system, and their role in drug resistance. This review will discuss tubulin/microtubule alterations associated with resistance to tubulin-binding agents. Novel antimicrotubule compounds that hold promise in the treatment of drug-resistant disease and are currently undergoing clinical evaluation will also be reviewed.