AbstractGuaifenesin, a widely used ingredient in over‐the‐counter cough and cold medications, has been a subject of debate regarding its efficacy in treating respiratory conditions. Despite its historical use and US Food and Drug Administration approval, recent studies have questioned its claimed expectorant effect and its effectiveness in managing symptoms. This article examines the available evidence, highlighting the lack of significant benefits over placebo for upper respiratory disease. The rationale for clinical use is examined alongside the potential downside and alternatives to recommending guaifenesin as a treatment option.