Stearoyl‐CoA desaturase 1 (SCD1) is an essential lipogenic enzyme that has been shown to play an intrinsic role in the development of obesity and related conditions, such as insulin resistance. Through the generation of various mouse models of SCD1 deficiency, we have come to understand that SCD1 plays a role, directly or indirectly, in diverse metabolic processes, including lipogenesis, fatty acid oxidation, insulin signaling, thermogenesis, and inflammation. This review will address recent advances in our understanding of this key regulator of cellular metabolic processes, including the role of SCD1 in maintaining skin barrier integrity and the role of skin SCD1 in the metabolic phenotype elicited by global SCD1 deficiency.