Retinol saturase (RetSat) is an oxidoreductase that is expressed in metabolically active tissues and is highly regulated in conditions related to insulin resistance and type 2 diabetes. Thus far, RetSat has been implicated in adipocyte differentiation, hepatic glucose and lipid metabolism, macrophage function, vision, and the generation of reactive oxygen species (ROS). Although initially described to transform retinol to 13,14-dihydroretinol, a function it was named after, alternative enzymatic reactions may underlie some of these biological effects. We summarize recent findings and identify major obstacles standing in the way of its pharmacological exploitation, how we might overcome these, and discuss the therapeutic potential of modulating the activity of RetSat in alleviating human pathologies.