Oxysterols are oxygenated derivatives of cholesterol that may be formed by either enzymatic or non-enzymatic mechanisms. Expression of the genes responsible for oxysterol synthesis (GROS) is known to be restricted across different tissues and cell types. Regulation of the transcription of GROS and the activity of their enzyme transcripts has been the subject of intense activity for many years. Recent studies have sought to decipher the mechanism(s) that underpin the restricted expression of the GROS. Available data indicates that epigenetic mechanisms have an important role to play in the control of the expression of GROS. In the current review we summarize the available evidence for the epigenetic regulation of these genes.