What transpires soon after inhaling Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the respiratory virus causing Coronavirus Disease 2019 (COVID-19)? Where does infection begin? What are the features of subsequent virus spread? How might host responses quickly contain infection? Two recently published manuscripts have evaluated infection in primary cultures of well-differentiated cells to address these questions and bring more light on the proviral and antiviral components operating during the initial days after SARS-CoV-2 exposure.