Cytochrome P450 enzymes (CYP, P450) are indispensable for human health and catalyse a plethora of reactions contributing to the clearance of xenobiotics, steroid and bile acid biosynthesis, and the functionalization of vitamins in the human body. The family of CYP4F fatty acid ω-hydroxylases consists of five isoforms, CYP4F2, CYP4F3A, CYP4F3B, CYP4F11 and CYP4F22, which share a high amino acid sequence similarity but assume different physiological functions in humans. While CYP4F2 and CYP4F3B are the major enzymes producing a lipid mediator from arachidonic acid, CYP4F3A inactivates leukotriene B4 as anti-inflammatory response, CYP4F11 is capable of effectively metabolizing drugs, and CYP4F22 contributes to a healthy skin barrier. In this review, we provide an overview of recent developments in CYP4F function and discuss potential future directions underlining their growing relevance in human health and disease.