Abstract The neurotoxicity of a variety of compounds may be uniquely expressed in their ability to disrupt cognitive function. The development of sophisticated behavioral tasks to assess cognitive and mnemonic function in rodents provides necessary tools for addressing these effects. The radial arm maze has been increasingly utilized to examine the psychological and neurobiological substrates of cognitive function. This paper critically examines the usefulness of this task in determining (1) the neurotoxicity of suspected neurotoxic compounds, (2) the neural systems which appear to be uniquely susceptible to a variety of toxicants and degenerative processes, and (3) the degree of behavioral and neural plasticity following neurotoxic insult. It is concluded that the radial arm maze provides an important tool that can be used to address several of the fundamental problems in neurotoxicology.