Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent of Coronavirus Infectious Disease 2019 (COVID-19), the most serious pandemic in a century. COVID-19 has caused more than 1.2 million deaths worldwide with the United States (US) leading the world in total cases and deaths. COVID-19 has critically strained economies, healthcare systems, and disrupted dental clinical practice, dental education, and research across the world. Despite signs of infection, including the presence of virus in saliva, oral-specific symptoms (loss of taste), and the potential for droplet and fomite transmission from the oral cavity, the involvement of the oral cavity in COVID-19 is poorly understood. Predominant research interest has focused on the nasal-lung axis COVID-19 pathogenesis and the development of a robust immune response; points critical to the development of efficacious vaccines which are now emminently on the horizon. However, critical to understanding the physiology of COVID-19, recent reports implicate the oral cavity as a key site of infection and transmission (Warner and Byrd, et al., 2020; Medrxiv). Pinpointing oral cell-specific tropism for SARS-CoV-2, establishing cell niches supportive of viral replication, and characterizing the potential for oral cavity secretions to spread within a host (e.g., oral-lung axis) or transmit extra-orally will undoubtedly extend our understanding of this disease and until we have a SARS-CoV-2 vaccine which is widely available, it is critical to support public health strategies to reduce risk such as universal mask wearing, social distancing, and hand hygiene. Moreover, deployment of established and novel dental infection control strategies to reduce the risk transmission are now being tested. Because the professions of dental hygiene and dentistry are among the most heavily impacted by COVID-19, it is prudent for dentistry/dental research to “lean in” and to take the lead in establishing the basic biology of the oral COVID-19 disease, novel and effective risk mitigation strategies, and promote evidence-based policy initiatives to promote safe clinical practice.