Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a newly emerged severe acute respiratory syndrome (SARS)-coronavirus-2 (SARS-CoV-2). COVID-19 presents a diverse clinical spectrum, ranging from an asymptomatic carrier state to patients with life-threatening multi-organ failure and death (Huang et al., 48a). The greatest risk factor for severe disease is age, with higher morbidity and mortality rates in the elderly population, despite younger people shedding similar levels of virus (Yanez et al., 104). The overall case fatality rate of COVID-19 is 2.3%, rising to 14.8% in patients over the age of 80, and 49% among the critically ill (Kang & Jung, 55). Currently, therapeutics for COVID-19 are limited. To overcome this, it is important that we use physiologically relevant models to reproduce the pathology of infection and evaluate the efficacy of antiviral drugs. Models of airway infection, including the use of a human infection challenge model or well-defined, disease relevant in vitro systems can help determine the key components that perpetuate the severity of the disease. Here, we briefly review the human models that are currently being used in COVID-19 research and drug development. This article is protected by copyright. All rights reserved.