DNA confined to nanofluidic channels with a cross-section from tens to hundreds of nm wide and hundreds of microns long stretches in an equilibrium process free of flow or end tethering. Because DNA is free to move along the channel axis, its extension is exquisitely sensitive to DNA-DNA interactions and the DNA persistence length, as well as the contour length. We discuss how this sensitivity has been used to probe DNA-protein interactions at physiological concentrations of both DNA and proteins.