The effect of Oleandrin is investigated on glioma growth in vivo. To this aim, SCID or C57BL/6 mice are transplanted, respectively, with human U87MG (5×10), U251, GBM19 (5×10), or murine (syngeneic) GL261 (7.5×10) cells into the right striatum and, after 10 d, treated daily with intraperitoneal Oleandrin for an additional 7 d. Oleandrin significantly reduces tumor sizes in human and murine glioma cell models in vivo in a dose-dependent way. High concentrations of Oleandrin (3 mg/kg) are fatal in both models, as expected from the known lethal dose for rodents. Doses of Oleandrin below the lethal dose (0.3 mg/kg) significantly increase the survival time from 32.6±1.4 d to 53.8±9.6 d in mice injected with U87MG cells (n=5-11; p<0.01, log-rank test) and from 23.37±1.2 d to 34.38±3.3 d (n=5-11; p<0.01, log rank test) in mice injected with GL261 cells.