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Viral respiratory infections (VRIs) are among the most common reasons for which primary care providers are consulted. VRIs due to rhinoviruses—the most commonly implicated etiologic agent—constitute a syndrome characterized by signs and symptoms of a cold. Rhinoviruses have been implicated in respiratory tract illnesses such as sinusitis and otitis media, as well as lower respiratory complications in high-risk populations. Most patients treat VRI with over-the-counter remedies that have been demonstrated to produce marginal clinical benefits. The development of novel antiviral agents has intensified interest in VRIs. Pleconaril, a capsid-function inhibitor currently under FDA review, has been shown in clinical trials to reduce the duration and severity of rhinovirus VRIs. By targeting the cause of illness, antiviral agents represent an opportunity to reduce the substantial clinical burden of VRI. Furthermore, effective therapies can potentially reduce inappropriate antibiotic use for viral infections.