Microtubules are dynamic cytoskeletal structures containing 13 protofilaments formed by αand β-tubulin dimers. These polymers are essential for numerous cellular processes, including cell division. Individual microtubules switch from growth to shortening and reverse both in vitro and in cells, a remarkable nonequilibrium behavior known as dynamic instability. The dynamic instability of microtubules is significantly accelerated during mitosis. Numerous drugs have been shown to inhibit the microtubule dynamics and thus inhibit cell division, leading to cell arrest at metaphase often followed by apoptosis. Some of these microtubule-targeting cytostatic drugs have been widely used for cancer treatment for several decades. The first clinically approved class of anticancer chemotherapy drugs was vinca alkaloids. These agents bind at the interface between tubulin dimers, inhibiting microtubule dynamics. In addition to vinca-binding site, at least five other binding pockets have been characterized on tubulins to date and more recently several new pockets have been identified. The two best characterized of these are the taxane site, located on the luminal side of the β-tubulin subunit, and the colchicine site, located in the intradimer interface of tubulin. Taxane site binders, such as paclitaxel and some of its analogues, were clinically approved in the 1990s and have been widely and successfully used to treat various types of cancers. The colchicine-binding site, named after a long-known drug derived from the plant Colchicum autumnale, is a very attractive and not yet clinically exploited anti-cancer target.