It is now well established that a reciprocal relationship exists between neurons and astrocytes, and that this association is vital for mutual differentiation, development, and functioning of both cell types. It had also become apparent that perturbations in astrocytic function may lead to deleterious consequences in juxtaposed neurons. It is therefore possible that neuronal damage induced by chemicals or neuropathic disease involves dissociation of astrocytic‐neuronal interactions. The purpose of this review is to explore astrocytic‐neuronal interactions, focusing on potential sites of neurotoxicant actions. In developing this thesis, we briefly examine the functional interactions between astrocytes and neurons, followed by specific examples of astrocyte‐mediated neurotoxicity.