Respiratory tract infections are a leading cause of death and disability and have remained the world’s most deadly communicable disease. Although the burden of respiratory infections decreased over the period of 1990-2019, the world encountered unprecedented challenges due to the COVID-19 pandemic, caused by the SARS-CoV-2 virus. Compared with prepandemic years, the United States experienced higher than usual hospitalizations, numerous shortages in supplies as well as personnel shortages, all of which resulted in increases in patient safety metrics, such as ventilator-associated pneumonia (VAP). Furthermore, advances in medicine, complex patient populations, and antimicrobial resistance have highlighted the continued need in understanding the pathogenesis of lung infections in the twenty-first century.