Traditionally, biomolecular systems have been studied in ensemble. While much can be determined with ensemble measurements, scientific and technological interest is rapidly moving to single-molecule techniques, which rely primarily on fluorescent markers and advanced microscopy techniques. In this paper, we describe recent work using nanoscale transistors based on carbon nanotubes as charge-sensitive detectors. We show carbon nanotubes can be used for ensemble studies through sidewall adsorption. Sensitivity can be greatly enhanced though an engineered defect in the nanotube. Biomolecular interactions are characterized by random-telegraph-noise response, which can be analyzed to study single-molecule kinetics and thermodynamics.