<p>Infections caused by respiratory viruses pose a&#xa0;major challenge to public health. While vaccines and in some cases therapeutics are now available for the “big&#xa0;3”: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza and respiratory syncytial virus (RSV), the preventive and treatment options for rhinoviruses, human metapneumovirus (hMPV), and human bocavirus (HBoV) remain limited. The SARS-CoV‑2 is currently endemic with seasonal fluctuations, which is currently dominated by omicron subvariants. The diagnostics by the polymerase chain reaction (PCR) remain the gold standard. Long coronavirus disease (COVID) represents an ongoing, interdisciplinary challenge. Influenza causes seasonally high morbidity and mortality, especially among high-risk groups and the recent transmission to mammals is a&#xa0;major cause of concern. The annually updated vaccines are of limited effectiveness due to low vaccination rates. Infections by RSV are traditionally considered a&#xa0;disease of early childhood but lead to increased morbidity and mortality, especially among the older population group. Newer prevention options are available but need to be better integrated into patient care. Rhinoviruses cause frequent, mostly mild infections but can trigger severe courses in chronically ill patients. Human metapneumoviruses are clinically relevant, particularly in young children but difficult to distinguish from other pathogens. Human bocavirus is frequently detected in children and is often part of coinfections. Overall, the differential diagnostics using multiplex PCR, remain crucial for clinical management. There is still a&#xa0;high need for research into many of these viruses with respect to surveillance as well as vaccination and treatment.</p>