About 100 trillion microorganisms compose the microbiome of the gastrointestinal tract and are predominantly found within the colon. Until recently, few bacteria were thought to inhabit the normal healthy esophagus and stomach. However, contemporary studies using molecular techniques have contradicted these assumptions. In this review, we summarize the pertinent findings of these studies that demonstrate established, complex mixed-microbial communities within the foregut in both health and disease. These studies contribute to improved understanding of interactions between the host immunity and the microbiome that may ultimately allow for novel therapeutic targets.