Upper respiratory tract infections (URTIs), primarily acute rhinopharyngitis, tonsillitis, adenoiditis, and rhinosinusitis (RS), are major causes of morbidity in both children and adults of any age. In addition to the frequent occurrence of related medical problems and the associated socioeconomic costs, URTIs have a significant impact on the quality of life of patients and their families, and have placed an escalating financial burden on the global healthcare system. Most URTIs are caused by viruses and require only symptomatic treatment. However, a number of cases, particularly those that are severe, recurrent, or chronic, have a bacterial etiology and need appropriate antimicrobial treatment to avoid complications or frequent exacerbations. To ensure therapeutic antibiotic concentration without any significant systemic drug exposure, the direct delivery of antibiotics to the upper respiratory tract by inhalation is a potential solution. The main aim of this review is to determine if and when aerosolized antibiotics can be effectively used to treat URTIs in noncystic fibrosis (non-CF) patients. There is a lack of strong evidence for the use of nebulized antibiotics to treat URTIs in non-CF patients. The only disease for which positive results have been reported is chronic RS in adults. However, conflicting conclusions have been drawn, and many problems related to the drug of choice, dosages, duration of treatment, and the best device for administration remain unsolved. Further studies are needed to better determine when and through which treatment modalities inhaled antibiotics can positively modify the course of chronic RS.