The microbiota of ripening cheese is dominated by lactic acid bacteria, which are either added as starters and adjunct cultures or originate from the production and processing environments (nonstarter or NSLAB). After curd formation and pressing, starters reach high numbers, but their viability then decreases due to lactose depletion, salt addition, and low pH and temperature. Starter autolysis releases cellular contents, including nutrients and enzymes, into the cheese matrix. During ripening, NSLAB may attain cell densities up to 8 log cfu per g after 3 to 9 mo. Depending on the species and strain, their metabolic activity may contribute to defects or inconsistency in cheese quality and to the development of typical cheese flavor. The availability of gene and genome sequences has enabled targeted detection of specific cheese microbes and their gene expression over the ripening period. Integrated systems biology is needed to combine the multiple perspectives of post-genomics technologies to elucidate the metabolic interactions among microorganisms. Future research should delve into the variation in cell physiology within the microbial populations, because spatial distribution within the cheese matrix will lead to microenvironments that could affect localized interactions of starters and NSLAB. Microbial community modeling can contribute to improving the efficiency and reduce the cost of food processes such as cheese ripening.