There is a large range of diseases, such diabetes and cancer, which are connected to abnormal fatty acid metabolism in human cells. Therefore, inhibitors of human fatty acid synthase have great potential to manage or treat these diseases. In prokaryotes, fatty acid synthesis is important for signaling, as well as providing starting materials for the synthesis of phospholipids, which are required for the formation of the cell membrane. Recently, there has been renewed interest in the development of new molecules that target bacterial fatty acid synthases for the treatment of bacterial diseases. In this review, we look at the differences and similarities between fatty acid synthesis in humans and bacteria and highlight various small molecules that have been shown to inhibit either the mammalian or bacterial fatty acid synthase or both.