To gain insight into regulatory processes involved in the biosynthesis of the clotting factor fibrinogen, which high plasma level is a risk factor for cardio vascular diseases, we studied novel mechanisms of transcriptional and post-transcriptional regulation of the three fibrinogen genes. We investigated the putative role of distant cis-regulatory sequences in the basal expression of the fibrinogen genes. The role of microRNAs, known to act as post-transcriptional regulators of gene expression, in the fine-tuning of fibrinogen production, has also been addressed. We identified a liver enhancer in the human fibrinogen gene cluster and discovered that miRNAs can influence fibrinogen expression. These studies add to the known mechanisms that control fibrinogen production and point towards potential cause of variable circulating fibrinogen levels. This work also demonstrates that all complex transcriptional and post-transcriptional mechanisms should be investigated in order to obtain a complete picture of the regulation of protein production.