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This review focuses on the cytotoxic effect of new synthetic pyrazolo[4,3-<i>e</i>][1,2,4]triazine derivatives against different tumor cell lines. Some annulated pyrazolotriazines i.e., pyrazolo[4,3-<i>e</i>][1,2,4]triazolo[4,3-<i>b</i>][1,2,4]triazines and pyrazolo[4,3-<i>e</i>]tetrazolo[1,5-<i>b</i>][1,2,4]triazine demonstrated significant broad cytotoxic activity in micromolar range concentration, which could have excellent potential to be new candidate therapeutic agents in cancer chemotherapy.