The transcriptional regulation of lipogenesis is a highly coordinated process occurring in concert with transcriptional as well as post-transcriptional regulation of enzymes involved in glycolysis and gluconeogenesis. Fatty acid synthase (FAS) plays a central role in de novo lipogenesis by converting acetyl-CoA and malonyl-CoA into the final end product, palmitate, which can subsequently be esterified into triacylglycerols and then stored in adipose tissue. Ultimately, this helps to prevent buildup of excess glucose in other types of cells and tissues, the effects of which can be readily observed in the pathophysiology of disease states such as Type-11 diabetes and obesity. Thus, elucidating the transcriptional mechanisms of lipogenic enzyme genes is important for understanding the normal regulation of lipogenesis and ultimately the dysregulation that may occur in certain metabolic disease. In this review, we discuss advances in our understanding of the regulation of lipogenesis at the genetic level, with a special emphasis on the common cis- and trans-acting factors involved in regulation of FAS. Two transcription factors, Upstream Stimulatory Factor (USF) and Sterol Regulatory Element Binding Protein-lc (SREBP-lc), seem to play a dominant and possibly cooperative role in regulating FAS transcription.