In 2022, COVID-19 remained the infectious disease at the top of most internal medicine physicians' minds. However, it was not the only infectious disease that was the topic of clinically relevant research that year. This article highlights some important infectious disease evidence unrelated to COVID-19 that was published in 2022. The literature was screened for sound new evidence relevant to internal medicine specialists and subspecialists whose focus of practice is not infectious diseases. The publications highlighted relate to various organisms in different patient populations. One article provides insight into the role of Helicobacter pylori eradication in the treatment of functional dyspepsia. The descriptive epidemiology of bacterial (Staphylococcus aureus) and viral (mpox) infections are the focus of 2 other articles. Several articles address the management of resistant and difficult-to-treat infections: multidrug-resistant gram-negative infections, resistant HIV-1, rifampin-resistant tuberculosis, cryptococcal meningitis, and invasive fungal infection in the setting of neutropenia. Another article provides data on effective HIV preexposure prophylaxis in women, an understudied population. Finally, given the urgent need to reduce inappropriate use of antibiotics, an article on antibiotic stewardship for hospitalized patients with presumed sepsis in a non-intensive care unit setting is also included.