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Natural drugs that interfere with the normal progression of mitosis belong to the most successful chemotherapeutic compounds currently used for anticancer treatment. These drugs affect the dynamics of the microtubules and cause the cellular death. Nevertheless, these drugs present limitations due to the adverse effects, the lack of selectivity and the development of resistances. Consequently, there is a particular interest to eliminate these limitations and the current researches have concentrated efforts in exploring novel mitotic targets that could offer therapeutic additional options for the patients of cancer. In this work, we summarize the molecular components of mitotic targets and the new strategies for anti-cancer therapy: kinesins (KSP/Eg5, CENP - E) and mitotic kinases (Auroras and PlK) besides cell cycle checkpoint abrogation during mitosis and at the G2/M transition inducing mitosisassociated tumor cell death. It is expected that this "next generation" of anti-mitotic drugs will be as successful as the classical anti-microtubule drugs, avoiding some of the limitations of these last. [ABSTRACT FROM AUTHOR]