Expression of the GFAP gene has attracted considerable attention because its onset is a marker for astrocyte development, its upregulation is a marker for reactive gliosis, and its predominance in astrocytes provides a tool for their genetic manipulation. The literature on GFAP regulation is voluminous, as almost any perturbation of development or homeostasis in the CNS will lead to changes in its expression. In this review, we limit our discussion to mechanisms proposed to regulate GFAP synthesis through a direct interaction with its gene or mRNA. Strengths and weaknesses of the supportive experimental findings are described, and suggestions made for additional studies. This review covers 15 transcription factors, DNA and histone methylation, and microRNAs. The complexity involved in regulating the expression of this intermediate filament protein suggests that GFAP function may vary among both astrocyte subtypes and other GFAP-expressing cells, as well as during development and in response to perturbations.