Despite guidelines and educational programs, systemic antibiotics and anti-inflammatory drugs are often inappropriately prescribed in upper respiratory tract infections (URTIs), although they are most often of viral origin, generally benign, and self-limiting with spontaneous recovery in more than 80% of cases. Reduced use of systemic antibiotics is crucial in the current context of concern about emerging antibiotic resistance and reducing unnecessary costs associated both with drug over-consumption and with the management of the consequences of antibiotic resistance. Local bacterial or viral infection of the airways induces an early inflammatory reaction. Although this inflammatory reaction has a beneficial effect in the capture and destruction of the pathogens, it can be responsible for deleterious tissue damage and vascular alterations leading to a self-perpetuating cycle of events. A wide array of medicines is available for symptomatic relief of URTIs: many of them are partially effective in reducing symptoms, but none is curative. Local administration of antibiotics and anti-inflammatory drugs allows drug delivery directly to the target site of infection and inflammation, i.e., the respiratory mucosa, thus enabling a higher concentration of the drug, which results in smaller doses to be given, decreased potential for systemic toxicity, fewer side effects, protection of other flora, and rapid relief. Fusafungine is a naturally occurring peptide antibiotic with anti-inflammatory properties, which selectively targets the tissue reaction and preserves the natural antibacterial and antiviral defences. It is indicated for topical use in nose and throat infections. A recent analysis of French general practitioners' (GPs) prescribing pattern in the field of URTIs has demonstrated that prescription of fusafungine has achieved what many educational programs have failed to do: a significant reduction in the 'real life' prescription of systemic antibiotics and antiinflammatory drugs, without the side effects of corticosteroids and vasoconstrictive agents, and without impact on microbial ecology.