OTO Open, Volume 6, Issue 2, April June 2022. Objective This review aimed to systematically determine the optimal nasal saline regimen for different types of sinonasal diseases. Data SourcesPubMed, Embase, SCOPUS, Cochrane Library, Web of Science, ClinicalTrials.gov. The last search was on December 6, 2021.Review Method Study selection was done by 2 independent authors. Randomized controlled trials and meta analyses were included. The effects of nasal saline treatment through various devices, saline tonicities, and buffer statuses were evaluated in patients with allergic and nonallergic rhinitis, acute and chronic rhinosinusitis (CRS), CRS with cystic fibrosis, and postoperative care, including septoplasty/turbinoplasty and endoscopic sinus surgery. Result Sixty nine studies were included: 10 meta analyses and 59 randomized controlled trials. For allergic rhinitis, large volume devices (≥60 mL) were effective for treating adults, while low volume devices (5 59 mL) were effective for children. Isotonic saline was preferred over hypertonic saline due to fewer adverse events. For acute rhinosinusitis, saline irrigation was beneficial in children, but it was an option for adults. Large volume devices were more effective, especially in the common cold subgroup. For CRS, large volume devices were effective for adults, but saline drop was the only regimen that had available data in children. Buffered isotonic saline was more tolerable than nonbuffered or hypertonic saline. The data for CRS with cystic fibrosis and nonallergic rhinitis were limited. For postoperative care, buffered isotonic saline delivered by large volume devices was effective. Conclusion Nasal saline treatment is recommended for treating most sinonasal diseases. Optimal delivery methods for each condition should be considered to achieve therapeutic effects of saline treatment.