The human gut is host to trillions of microbes that from birth begin interacting with our immune system. Over time this relationship is thought to shape critical aspects of human function such as metabolism, brain development, immune response, and overall gut health. Recent advances in technology have allowed us to begin understanding this complex relationship and have demonstrated that microbes within the gut ecosystem can be influenced by a variety of factors including mode of delivery, diet, and medication exposure, all of which can impact host health in either positive or detrimental ways. Perturbations of gut homeostasis have been implicated in many forms of digestive disease such as inflammatory bowel disease, irritable bowel syndrome, Helicobacter pylori infection, and even in cases of antibiotic-associated diarrhea. As such, researchers have sought methods to either restore gut homeostasis or prevent dysregulation of the gut community, also known as dysbiosis, through an emerging field known as microbial therapeutics. Examples of existing modalities are reviewed here such as prebiotics, probiotics, fecal microbial transplantation, and dietary therapy. As these therapies become further substantiated through research and increasingly desired by patients and their families, there is a need for providers caring for children to familiarize themselves with the existing data and indications for use. As we look to the future, machine-learning algorithms and more readily available next-generation sequencing of fecal samples may allow us to harness data from a person's gut microbiota to predict response to a particular intervention and tailor therapeutic options with an aim toward precision medicine. [Pediatr Ann. 2021;50(8):e336-e342.].