Streptococcus salivarius K12 (S. salivarius K12) is a pioneering probiotic strain derived from the human oral microbiota, known for its unique ability to enhance oral and upper respiratory tract health. This comprehensive review explores the background, mechanism of action, clinical applications, limitations, and evidence-based use of S. salivarius K12, with a special focus on its role in pediatrics. Evidence suggests that S. salivarius K12 helps reduce the incidence of upper respiratory tract infections (URTIs), otitis media, halitosis, and dental caries. Despite its promising benefits, challenges such as short-term colonization and variability in efficacy warrant further investigation.