Clinical intervention in neurological disorders is almost invariably achieved using chemical agents that act on neuromediator-related sites, suggesting that intercellular chemical signaling plays a major role in determining the properties of neural networks. A variety of microvoltammetric sensors and techniques have been developed over the last 25 years to study neuromediators in intact brain in vivo, and in isolated tissues, for animal models of behavior and disease. This review, with over 600 citations, considers the advantages and limitations of the different approaches, including progress in biosensor design, illustrated by studies on the neurochemical bases of a wide variety of behaviors.