Estramustine (EM), a conjugate of nornitrogen mustard and estradiol, is a antimicrotubule drug currently in use for the treatment of advanced prostatic carcinoma. Experimental data are accumulating concerning the antitumor effect of EM in other malignancies, and clinical studies in other malignancies are ongoing. This review summarizes the information available to date concerning the effects of EM and the development of drug resistance. EM depolymerizes microtubules by binding to microtubule-associated proteins (MAPs) as well as tubulin. Because of the radiosensitizing effect of this drug there has been a recent increase in interest concerning estramustine and its clinical use. Recently, it was proposed that EM induces an apoptotic cell death in glioma cells in vitro and in a rat model. EM resistance is distinct from MDR phenotype; it has been used in combination with antimitotic agents which are part of the MDR phenotype. Observations made with estramustine-resistant cell lines show the acquisition of estramustine resistance is a function of multiple adaptation by changes at tubulin expression pattern, and is also associated with changes in tau expression and phosphorylation.