Modulation of the microbiota for restoring and maintaining health is a growing issue in medical science. A search for relevant clinical trials on the use of probiotic bacteria as a potential and clinically applicable anti-caries measure was performed. According to predetermined criteria, papers were selected and key data on study design, sample size, intervention, duration, and results were extracted. Two animal and 19 human studies were retrieved. Most studies were short-term and restricted to microbiological endpoints, and only 3 human studies reported a caries endpoint. A high degree of heterogeneity among the included investigations hampered the analysis. Significant reductions of mutans streptococci in saliva or plaque following daily intake of probiotic lactobacilli or bifidobacteria were reported in 12 out of 19 papers, whereas 3 reported an increase of lactobacilli. Three caries trials in preschool children and the elderly demonstrated prevented fractions of between 21% and 75% following regular intakes of milk supplemented with L. rhamnosus. No adverse effects or potential risks were reported. The currently available literature does not exclude the possibility that probiotic bacteria can interfere with the oral biofilm, but any clinical recommendation would be premature. Large-scale clinical studies with orally derived specific anti-caries candidates are still lacking.