The ways in which gene transcription is investigated have undergone radical change since the turn of the millennium. Piece-meal approaches focussed upon model genes have increasingly been complemented by genome-wide approaches that allow interrogation of multiple cohorts of genes or even entire genomes. This sea change has been founded upon the increasing availability of whole genome sequences and the attendant evolution of microarray based discovery platforms. Collectively, these approaches are being used to build a global and dynamic perspective of transcription factor occupancy, co-factor recruitment and epigenetic signature. As yet, few of these approaches have been applied to the study of neuronal gene transcription, but this is set to change. Here, I review these key developments and point to their potential application to the study of transcriptional and epigenetic changes in neurons in health and disease.