Regulation of gene expression by nuclear receptors and transcription factors involves the concerted action of multiple proteins. The process of transcriptional activation involves chromatin modification, nuclear receptor or transcription factor binding to the response element of the promoter, and coregulator recruitment. Despite advances in knowledge pertaining to the molecular mechanisms of gene regulation overall, there is very limited information available on the molecular mechanism of lactoferrin gene regulation. This review will outline novel information relating to general gene regulation and will discuss the current understanding of the regulation of lactoferrin gene expression by nuclear receptors and transcription factors.