We investigate self-assembled DNA monolayers on metal and dielectric supports. Chains ranging in size from oligonucleotides to gene-sized polymers have been site-specifically attached without detectable side reactions in an end-tethered, "polymer brush" geometry. On metal supports, polythiol-mediated anchoring can be used to provide highly permanent immobilization of the nucleic acid. X-ray photoelectron spectroscopy (XPS), dynamic light scattering, and electrochemical methods have been applied to investigate the charging behavior, counterion partitioning, and organization of DNA monolayers on metal supports, and to evaluate label-free electrochemical approaches for monitoring interfacial hybridization reactions. The interfacial capacitance of end-tethered DNA films has been interpreted within a polyelectrolyte brush model. The observed trends with ionic strength and strand surface coverage generally agree with physical expectations, although as yet not understood increase in capacitance with decrease in ionic strength is observed for densest monolayers. Diagnostic applications are being pursued through development of near-field imaging methods and of active microelectronic substrates that integrate signal detection and processing functionality "on-chip." Near-field measurements offer a label-free technique with a sensitivity comparable to that of fluorescence-based systems currently in widespread use. Microelectronic biochips replace costly macroscopic instrumentation by integration of equivalent function within the solid support, using affordable CMOS microfabrication. Results from validation studies of these emerging technologies and their promise for more portable, simplified, and economical assays will be also described.