The changing logic of chemotherapy: metronomic dosing at lower levels, in combination with other agents. The conventional logic of chemotherapy has been to treat cancers with closely spaced bolus infusions of drugs at or near the MTD, followed by substantial rest periods. The typical results were transitory improvements in tumor burden and life-span extension accompanied by disturbing side effects and eventual relapse. The new logic of chemotherapy involves dosing at constant intervals without rest periods (metronomic scheduling), the use of lower doses to minimize toxic side effects and eliminate the obligatory rest periods, and combination with other drugs targeting distinct aspects of a cancer’s functionality. The metronomic and combinatorial dosing strategies can kill tumor endothelial cells as well as overt cancer cells and, perhaps, other cellular constituents of a tumor, offering the prospect for genuine efficacy. The bullets refer to doses of chemotherapy, which can be large and episodic (upper scheme) or smaller and metronomic (lower); the bombs indicate other anti-cancer agents providing additive or synergistic benefits.