The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute coronavirus type 2 (SARS-CoV-2), has significantly affected the lives of many people across North Carolina and the United States. Similar to the rest of the country, the epidemiology of SARS-CoV-2 in the state indicates health disparities among Black and Hispanic/Latino individuals, the presence of hotspots, or counties with high numbers of infected persons, and clusters of transmission among congregate living facilities. There have been many advances in diagnostic methods for SARS-CoV-2 and therapies for hospitalized patients nationwide. Public health strategies have included widespread testing for SARS-CoV-2, optimal management of cases, contact tracing efforts, and a phased reopening of sectors/activities in North Carolina with masks and physical distancing to minimize spread of the virus. In this issue, several authors, researchers, and public health leaders discuss the challenges that North Carolinians have experienced with respect to COVID-19 and several factors that are likely contributing to the health disparities among racial/ethnic minorities who have had the highest number of cases and deaths from SARS-CoV-2. Additional strategies also reported in this issue include the use of strike teams and mobile units to reach populations at high risk for infection and severe illness. Promoting individual and population-level strategies for minimizing transmission of SARS-CoV-2, especially among the most vulnerable, and consistent public health messaging based on science are critical as we face the new year and continued uncertainties around the COVID-19 pandemic.