Bifidobacteria and lactobacilli are widely exploited as health-promoting bacteria in many functional foods. However, the molecular mechanisms as to how these bacteria positively impact on host health are far from completely understood. For this reason these microorganisms represent a growing area of interest with respect to their genomics, molecular biology and genetics. Recent genome sequencing of a large number of strains of bifidobacteria and lactobacilli has allowed access to the complete genetic makeup of representative members of these bacteria. Here, we will discuss how the analysis of genomic data has helped us to understand the mechanisms by which these bacteria adapt to the specific environment of the gastrointestinal tract, while also revealing genetic functions that mediate specific host-microbe interactions.Bifidobacteria and lactobacilli are widely exploited as health-promoting bacteria in many functional foods. However, the molecular mechanisms as to how these bacteria positively impact on host health are far from completely understood. For this reason these microorganisms represent a growing area of interest with respect to their genomics, molecular biology and genetics. Recent genome sequencing of a large number of strains of bifidobacteria and lactobacilli has allowed access to the complete genetic makeup of representative members of these bacteria. Here, we will discuss how the analysis of genomic data has helped us to understand the mechanisms by which these bacteria adapt to the specific environment of the gastrointestinal tract, while also revealing genetic functions that mediate specific host-microbe interactions.