Well over half the mass of microtubules is composed of the protein tubulin, and interference with the functions of tubulin in cells can lead to profound disturbances of cellular physiology. Since the mitotic spindle is largely composed of microtubules, one of the most dramatic consequences of microtubule disruption is metaphase arrest. Condensed chromosomes are unable to progress through mitosis because the spindle fails to form. Besides the extensive protein-protein interactions required for microtubule assembly, tubulin interacts as well with numerous small molecules; these latter interactions are important both for understanding the mechanism of microtubule assembly and for devising pharmacologically relevant means for interfering with this process. This latter goal is of particular interest because antimitotic agents already have important, although relatively limited, roles in the treatment of neoplastic and inflammatory diseases. Although tubulin clearly interacts with molecules which are normally thought to represent solvent components (e.g., glycerol, 1-3 glutamate, 4,5 sulfonate buffers 6,7 ), this article is restricted to three classes of agent — nucleotides, divalent cations, and antimitotic drugs — which are of most importance in the structure, function, and control of tubulin physiology and offer obvious potential for manipulating the protein to gain a greater understanding of its intracellular roles.