Exposure to various chemicals and environmental hazards elicits changes in the expression of a variety of genes. The study of gene expression and transcriptional regulation is an important aspect of understanding the mechanisms associated with neurotoxicity. The availability of whole genome sequences and the development of new tools to identify and monitor transcriptional activity have accelerated the rate of discovery. This review surveys the historical steps taken to study gene expression in the brain and deals with recent advances in our understanding and classification of the roles of transcription factors. Disturbances in the regulation of gene expression associated with the neurotoxic response are also presented. Specific focus and detail is presented on the effects of heavy metals on the integrity and function of zinc finger proteins.