Objective The advent of high-throughput sequencing and ‘omic’ technologies is facilitating an ‘open-ended’ understanding of the human microbial community and its interplay with health. This commentary aims to present key perspectives and summarize current evidence from metagenomic studies of salivary microbiota in relation to general health and systemic diseases. Design A narrative review of studies that described salivary microbiome composition in relation to various general health conditions was conducted and the main results were summarized. Results Currently available evidence shows salivary microbial patterns and fingerprints as related to a range of metabolic, autoimmune and immunodeficiency associated conditions, similar to albeit at a far lower scale than similar studies in the gut microbiome. Conclusions Considering the relative ease of collection, emerging evidence of association with non-oral diseases may imply that saliva microbiome research may have potential diagnostic or prognostic value. [ABSTRACT FROM AUTHOR]