Viruses infecting vertebrate hosts must overcome the interferon (IFN)-mediated antiviral response to replicate and propagate to new hosts. The complex regulation of the IFN response allows viruses to antagonize IFN at multiple levels. However, no single strategy appears to be the golden ticket, and viruses have adopted multiple means to dampen this host defense. This Review does not exhaustively cover all mechanisms of viral IFN antagonism. Rather it examines the ten most common strategies that viruses use to subvert the IFN response with examples from publications appearing in the last 10 years of Cell Host & Microbe. The virus-host interactions involved in induction and evasion of IFN represent a fertile area of research due to the significant large number of host and viral products that regulate this response, resulting in an intricate dance between hosts and their pathogens to achieve an optimal balance between virus replication, host disease, and survival. Viruses are formidable pathogens that take advantage of the infected cell machinery while disarming the antiviral host defenses. García-Sastre reviews the most common mechanisms used by viruses to antagonize the antiviral interferon response, illustrating the complexity of pathways that sense viral infection and regulate antiviral innate immune responses.