Viperin is an interferon (IFN)-stimulated gene product, which is part of the first line of the intracellular response against viral infection. It is a potent antiviral protein, strongly upregulated after IFN-stimulation and virus infection. Viperin is antivirally active against many different viruses from different families and has been shown to inhibit several flaviviruses. Flaviviruses are an important group of arthropod-borne viruses that cause millions of infections annually. In this review, we focus on the recent advances of the antiviral mechanisms of viperin against these flaviviruses, both pointing to similarities and differences between viruses within the same genera.