How does SARS-CoV-2 evade our immune defenses? It’s a good question, actually. When SARS-CoV-2 defeats host defenses, we need to know how it does so, and conversely, when host defenses prevail, that also needs to be understood. The first time that a cell meets the virus, it is the local innate immune system inside the infected cell that must spring into action. By the time more diffuse bloodborne signaling and other system-wide adaptive immune responses unfold, it may be too late.