Electric fields excite electrically active tissue by several mechanisms. A long, straight, uniform fiber is polarized by an activating function, proportional to the axial gradient of the axial electric field. During unipolar anodal stimulation, the activating function results in two areas of depolarization (virtual cathodes) that are responsible for anode-make stimulation. During unipolar cathodal stimulation, the virtual anodes can be exploited to produce unidirectional propagation and physiological recruitment of axons. Anode-break stimulation of nerves arises from the intrinsic properties of the sodium channel kinetics; cathode-break stimulation in nerves is anode-break stimulation at a virtual anode. The activating function applies to magnetic stimulation as well as to electric stimulation. Other important mechanisms of stimulation arise if the fiber is terminated, nonuniform, or curved. In the brain, cortical neurons are excited when the electric field is directed from the dendrites toward the axon. Possible mechanisms for cortical excitation are the impedance mismatch between the axon and dendritic tree, and the axon bending as it enters the white matter. Transcranial magnetic stimulation differs from transcranial electric stimulation because during magnetic stimulation the electric field is parallel to the brain surface, whereas during electric stimulation the electric field has components both parallel and perpendicular to the brain surface. Cardiac tissue can be represented by use of the bidomain model. This model predicts that a point-source stimulus results in adjacent areas of depolarized and hyperpolarized tissue. The presence of virtual anodes during cathodal stimulation is analogous to the creation of virtual anodes along a one-dimensional fiber by the activating function. Anode- and cathode-break stimulation both occur in cardiac tissue, but the mechanism may be different than for nerve and may depend on diffusion of depolarization into a previously hyperpolarized region. Electrical stimulation of cardiac tissue can cause reentry through a critical point mechanism. Two mechanisms for defibrillation have been hypothesized: (1) the relatively high junctional resistance between cardiac cells causes each cell to be depolarized on one side and hyperpolarized on the other; and (2) the fiber tracts within the heart behave like individual fibers, with fiber curvature providing a mechanism for polarization. Similarities among nerve, brain, and cardiac stimulation are emphasized.