DNA intercalating antitumor agents represent one of the more widely used classes of therapeutic agents in clinical oncology. Although a decisive mechanism to explain their ability to kill tumor cells has not been fully defined, the past decade has shown vast progress toward identifying key possibilities. The anthracenediones and anthrapyrazoles represent two latter generation classes of DNA intercalators that show great clinical promise as antitumor drugs. This article will review the currently known biochemical pharmacology for these agents and integrate these data into a broader picture touching on mechanisms of tumor cell kill.