Baroreceptors sense and signal the central nervous system of changes in arterial pressure through a series of sensory processes. An increase in arterial pressure causes vascular distension and baroreceptor deformation, the magnitude of which depends on the mechanical viscoelastic properties of the vessel wall. Classic methods (e.g., isolated carotid sinus preparation) and new approaches, including studies of isolated baroreceptor neurons in culture, gene transfer using viral vectors, and genetically modified mice have been used to define the cellular and molecular mechanisms that determine baroreceptor sensitivity. Deformation depolarizes the nerve endings by opening a new class of mechanosensitive Ion channel. This depolarization triggers action potential discharge through opening of voltage-dependent sodium (Na+) and potassium (K+) channels at the "spike initiating zone" (SIZ) near the sensory terminals. The resulting baroreceptor activity and its sensitivity to changes in pressure are modulated through a variety of mechanisms that influence these sensory processes. Modulation of voltage-dependent Na+ and K+ channels and the Na+ pump at the SIZ by membrance potential, action potential discharge, and chemical autocrine and paracrine factors are important mechanisms contributing to changes in baroreceptor sensitivity during sustained increases in arterial pressure and in pathological states associated with endothelial dysfunction, oxidative stress, and platelet activation.