A large body of evidence suggests that single- and multiple-strain probiotics and synbiotics could have roles in the management of specific gastrointestinal disorders. However, ongoing concerns regarding the quality and heterogeneity of the clinical data, safety in vulnerable populations, and the lack of regulation of products containing live microbes are barriers to widespread clinical use. Safety and regulatory issues must be addressed and new technologies considered. One alternative future strategy is the use of synthetic bacterial communities, defined as manually assembled consortia of two or more bacteria originally derived from the human gastrointestinal tract. Synthetic bacterial communities can model functional, ecological, and structural aspects of native communities within the gastrointestinal tract, occupying varying nutritional niches and providing the host with a stable, robust, and diverse gut microbiota that can prevent pathobiont colonization by way of colonization resistance. Alternatively, phage therapy is the use of lytic phage to treat bacterial infections. The rise of antimicrobial resistance has led to renewed interest in phage therapy, and the high specificity of phages for their hosts has spurred interest in using phage-based approaches to precisely modulate the microbiome. In this Review, we consider the present and future of microbiome-targeting therapies, with a special focus on early-life applications, such as prevention of necrotizing enterocolitis.