Divalent ions like zinc, in its chelatable form, are found ubiquitously in all tissues in the mammalian body. Its amount varies and in some tissues, such as certain areas of the brain and the gastrointestinal tract, it may reach hundreds of micromolar in a specific compartment. Physiological as well as pathological conditions can lead to large changes in both the extra- and intracellular concentration of this ion. Zinc modulates, enhances or inhibits many channels in the course of physiological activity as in the hippocampus or during pathological incidents such as during ischemic episodes. In this chapter we have tried to outline the effect on some of the channels modulated by zinc. Channel modulation is achieved by the slow permeation of zinc through the channel or, like in most cases, due to binding of zinc to specific sites on the channel proteins. We concentrated on major mono and divalent ligand or voltage gated cationic channels since space was not allowed to discuss all the channels, including anionic and non ionic channels modulated by zinc.