Significant progress has been made over the past few years in studies of drug-DNA interactions. Structure-based design strategies have yielded new DNA-binding agents with clinical promise. The hairpin polyamides represent the result of a design strategy with outstanding potential. One specific molecule of this class has now been proven to inhibit the expression of a specific gene in vivo. A new bisintercalating anthracycline antibiotic binds with high affinity to DNA, and appears to overcome a specific form of multidrug resistance. Progress in fundamental studies of drug binding to DNA continues, with detailed thermodynamic studies providing new insights into the forces that drive complex formation. New tools have been developed in order to characterize both the binding mode and the sequence specificity of drug binding to DNA, tools that will enable the fundamental aspects of these biologically important reactions to be understood in more detail.