Lactobacillus salivarius has been frequently isolated from the mammalian digestive tract and has been studied as a candidate probiotic. Research to date has described the immunomodulatory properties of the species in cell-lines, mice, rats and humans for the alleviation of intestinal disease and the promotion of host well-being. The ability of L. salivarius to inhibit pathogens and tolerate host antimicrobial defenses demonstrates the adaptation of this species to the gastrointestinal niche. L. salivarius is the best characterized of 25 species in the L. salivarius clade of the genus Lactobacillus. Several other species of this clade are candidate probiotics; however, their probiotic potential has not yet been exploited. This review summarizes the research defining the probiotic nature of L. salivarius, by focusing in particular on L. salivarius UCC118 as a representative strain. The emergent research detailing the probiotic potential of other species in this phylogenetic clade will also be discussed.