Infection with SARS-CoV-2 frequently commences in the nasal cavity, yet knowledge about this initial virus-host interaction is sparse. In this review, we update our current understanding of SARS-CoV-2 infection via the nasal epithelium and the associated local immune response. Furthermore, we present considerations to how this interaction may influence the clinical course of COVID-19 and the systemic immune response, and lastly touch upon the potential for intranasal vaccination, intranasal antiviral therapies and immunomodulatory approaches.