Nitric oxide is an endogenous molecule that plays a role of second messenger in the central and peripheral nervous system. A major action of this molecule is to control ionic channel activity. Because of technical difficulties to use nitric oxide as a gaseous compound, nitric oxide donors are often utilized under controlled experimental conditions. Here we will review the advantages and limitations in using these compounds. Nitric oxide can affect ionic channels through direct interactions or through the production of cGMP. We will describe an example of direct action of nitric oxide on glutamate-gated channels. We will also review indirect actions of nitric oxide on various potassium and calcium channels. Finally, we will discuss the complex physiological consequences of the action of nitric oxide on these ionic channels.