Gene-environment interactions underlie cancer susceptibility and progression. Yet, we still have limited knowledge of which environmental factors are important and how they function during tumorigenesis. In this respect, the microbial communities that inhabit our gastrointestinal tract and other body sites have been unappreciated until recently. However, our microbiota are environmental factors that we are exposed to continuously, and human microbiome studies have revealed significant differences in the relative abundance of certain microbes in cancer cases compared with controls. To characterize the function of microbiota in carcinogenesis, mouse models of cancer have been treated with antibiotics. They have also been maintained in a germfree state or have been colonized with specific bacteria in specialized (gnotobiotic) facilities. These studies demonstrate that microbiota can increase or decrease cancer susceptibility and progression by diverse mechanisms such as by modulating inflammation, influencing the genomic stability of host cells and producing metabolites that function as histone deacetylase inhibitors to epigenetically regulate host gene expression. One might consider microbiota as tractable environmental factors because they are highly quantifiable and relatively stable within an individual compared with our exposures to external agents. At the same time, however, diet can modulate the composition of microbial communities within our gut, and this supports the idea that probiotics and prebiotics can be effective chemoprevention strategies. The trajectory of where the current work is headed suggests that microbiota will continue to provide insight into the basic mechanisms of carcinogenesis and that microbiota will also become targets for therapeutic intervention.