The host restriction factor Tetherin is an interferon-inducible typeⅡ membrane glycoprotein, and plays a vital role in retroviral life cycle. The unusual topology of Tetherin is important for its antiviral activity. Tetherin restricts viral replication by inhibiting enveloped virus release from the surface of infected cells. However, viruses have evolved different strategies to antagonize the antiviral action of Tetherin. The interaction between Tetherin and its antagonist is species-specific which evidenced a long term co-evolution during the fighting history between host and viruses. In this review, we focus on the current advances in our understanding of the molecular structure and antiviral activity of Tetherin, as well as the mechanism used to conteract Tetherin by its antagonists.