The laryngopharyngeal reflux disease (LPRD) treatment remains controversial due to the poor effectiveness of proton pump inhibitors (PPIs). In this paper, the author reviewed the current primary treatments used in clinical studies for managing LPRD and discussed the pharmacological, biological, and physiological properties of medication for providing clinical relevance for otolaryngological practice. A comprehensive review of the PubMed, Cochrane Library, and Scopus literature was conducted to document and analyze the medical treatments of LPRD in the largest case series published in the past 20 years. Fifty-five studies met the inclusion criteria, revealing that 67 different therapeutic regimens were used in the LPRD studies in the past 20 years with nine different therapeutic durations. PPIs have been used as a single therapy in 70.1% of cases. PPIs were combined with another drug in 23.9% of cases. Alginates and antacids were used as single therapy or in association with other drugs in 10.5% and 3.0% of cases, respectively. There was an important variability of molecules, doses, and regimens. There is an important gap between current therapeutic practice and the recent advancements in the pathophysiology of LPRD. The pharmacological and physiological findings of this review can reasonably support the notion that alternative gastroesophageal reflux disease therapies (alginate, antacids) could take a significant place in the treatment of primary or recalcitrant LPRD. Future studies are needed to confirm the stability of the LPRD profile at the hypopharyngeal-esophageal multichannel intraluminal impedance-pH and the role of digestive enzymes in the development of upper aerodigestive tract mucosa inflammation and symptoms.