Epothilones are naturally occurring 16-membered macrolides with the ability to promote tubulin polymerization in vitro and to stabilize preformed microtubules against Ca2+- or cold-induced depolymerization. In contrast to paclitaxel (Taxol) epothilones are also active in vitro against multidrugresistant cancer cell lines as well as cell lines whose paclitaxel-resistance is derived from specific β-tubulin mutations. Based on their attractive in vitro biological profile epothilones have turned into important lead structures in anticancer drug discovery and hundreds of analogs and derivatives of epothilone A and B have been prepared and biologically characterized over the past four years. A number of compounds, including natural epothilone B, deoxyepothilone B, and epothilone B lactam (BMS-247550) have also been reported to exhibit profound in vivo antitumor activity in animal models. Apart from providing a brief summary of the SAR that has emerged from the above in vitro studies, this minireview will largely focus on the biology and chemistry of those analogs for which in vivo antitumor activity has been reported in the literature. Two of these compounds, natural epothilone B and epothilone B lactam (BMS-247550) have advanced to clinical studies in humans.