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Ovarian cancer is the most lethal gynecologic malignancy worldwide with extremely poor patient prognosis. Elucidation of the detailed mechanisms of action of drugs targeting this cancer type is necessary to optimize treatment efficacy. Epothilones, a new class of microtubule-stabilizing anticancer drugs, show strong cytotoxic properties in vitro and in vivo and are additionally effective in taxane-resistant cells. In this report, we focus on inhibitors of microtubule depolymerization, taxanes, and the novel antimicrotubule agents, epothilones. Current knowledge regarding the effects of epothilone B on ovarian tumor cell metabolism is reviewed, along with recent advances in therapeutic strategies, such as novel agents and biologic drug combinations containing epothilone that target aberrant pathways in ovarian cancer.