Fluvirucins are bioactive macrolactam glycosides isolated from actinomycetes. This review gives an overview of this family of natural products, covering isolation, biological activities, biosynthesis, and total synthesis. The synthesis of fluvirucins and their aglycons, the fluvirucinins, is presented, paying special attention to the synthetic strategy and stereochemical aspects. 1 Introduction 2 Isolation, Biological Activity, and Biosynthesis 3 Synthetic Approaches 3.1 Closure of the 14-Membered Ring by Ring-Closing Metathesis 3.2 Closure of the 14-Membered Ring by Macrolactamization 3.3 Construction of the 14-Membered Ring by Aza-Claisen Ring Expansion 4 Conclusion