Interferon-gamma, a type II interferon, is an important immunoregulatory molecule whose initial biological properties were first reported in 1965. Although the effects of IFN gamma in vitro and in vive and at the molecular level have been widely investigated, the transcriptional control of this single copy gene has not been as extensively studied. In this review I will attempt to summarize what is known about the role of DNA binding proteins and genomic DNA regulatory regions in the regulation of transcription of the IFN gamma gene. Current data suggests that transcriptional regulation involves DNA methylation and the interaction of multiple different DNA binding proteins with both promoter and intronic enhancer and suppressor elements.