Microtubules and actin filaments play important roles in mitosis, cell signaling, and motility. Thus these cytoskeletal filaments are the targets of a growing number of anti-cancer drugs. In this review we summarize the current understanding of the mechanisms of these drugs in relation to microtubule and actin filament polymerization and dynamics. In addition, we outline how, by targeting microtubules, drugs inhibit cell proliferation by blocking mitosis at the mitotic checkpoint and inducing apoptosis. The β-tubulin isotype specificities of new anticancer drugs and the antitumor potential of agents that act on the actin cytoskeleton are also discussed.