A collection of useful molecular techniques to illuminate and explore the interaction of drugs and ligands with DNA. These easily reproducible methods involve sequence recognition properties, as well as the physical approaches for measuring both the strength of interaction and the mode of drug binding to DNA. The interactions are also examined from a cellular perspective and for their usefulness in the design of new therapeutic agents. The powerful techniques detailed here will be particularly useful in elucidating the action of existing therapeutic agents, as well as in the design of new anti-cancer drugs with improved action and reduced toxicity.