Colchicine exerts its biological effects through binding to the soluble tubulin heterodimer, the major component of the microtubule. The colchicine-binding abilities of tubulins from a variety of sources are summarized, and the mechanism of colchicine binding to brain tubulin is explored in depth. The relationship between colchicinoid structure and tubulin binding activity provides insight into the structural features of colchicine responsible for high affinity binding to tubulin and is reviewed for analogs in the colchicine series. The thermodynamic and kinetic aspects of the association are described and evaluated in terms of the binding mechanism. Colchicine binding to tubulin results in unusual alterations in the low energy electronic spectra of colchicine. The spectroscopic features of colchicine bound to tubulin are discussed in terms of the nature of the colchicine-tubulin complex. Attempts to locate the high affinity colchicine binding site on tubulin are presented.