In the past 20 years, we have experienced a growing and innovative field investigating the vast human microbiota and its influence on health and disease pathogenesis. From this, we anticipate new prevention and therapeutic strategies for an increasing number of cancer types. In most cancers, microbiome research has flourished over the last 5–10 years. This is aptly illustrated in this issue of Cancer and Metastasis Reviews which contains important discussions of the findings and impact of microbiome research across colon, esophageal, pancreatic, and lung cancers, as well as melanoma, multiple myeloma, and hematopoietic malignancies. These papers discuss important cancer microbiome associations—local, systemic, and/or cancer-specific—and an early appreciation of mechanistic mediators focusing on immune responses, microbial metabolites, and/or the tumor microenvironment as well as responses to immunotherapy.