Inhibition of mitosis is a useful strategy for treating diseases involving excessive cell proliferation. Antimitotic drugs currently in clinical use perturb microtubule dynamics and thereby disrupt the function of the mitotic spindle. Protein regulators of microtubule dynamics and microtubule motors are also essential for mitotic spindle function. In this chapter, we evaluate the potential of these proteins as candidate targets for antimitotic drugs. We review in depth a number of proteins of particular interest, highlighting their known functions in mitosis and the effects of their inhibition on cell cycle progression.