Much interest has been generated in the lay and scientific press regarding the microbiome in human health and disease. This coverage is most certainly warranted and represents one of the most exciting and rapidly developing fields in research that has the great potential to help the medical community understand and treat human disease. Because the specialty of surgery is so integrally related to the treatment of many benign and malignant diseases, addressing the intersection of the microbiome with surgical diseases is critical. The chapter will provide the reader who is interested in this topic, a framework for discussion and further independent reading through the comprehensive reference list of notable studies. While there is limited discussion of microbial taxonomic changes in order to maintain an approachable narrative to all readers, the astute reader will notice themes and trends in bacterial taxa discussed in this review. In this chapter, a broad overview is presented on the microbiome, methodologies to investigate and conduct microbiome studies, the role of the microbiome in surgical health and disease, and areas of future investigation to advance this exciting and critical field.